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Strength Training Increases Insulin-Mediated Glucose Uptake, GLUT4 Content, and Insulin Signaling in Skeletal Muscle in Patients With Type 2 Diabetes
Abstract
Strength training represents an alternative to endurance training for patients with type 2 diabetes. Little is known about the effect on insulin action and key proteins in skeletal muscle, and the necessary volume of strength training is unknown. A total of 10 type 2 diabetic subjects and 7 healthy men (control subjects) strength-trained one leg three times per week for 6 weeks while the other leg remained untrained. Each session lasted no more than 30 min. After strength training, muscle biopsies were obtained, and an isogly-cemic-hyperinsulinemic clamp combined with arterio-femoral venous catheterization of both legs was carried out. In general, qualitatively similar responses were obtained in both groups. During the clamp, leg blood flow was higher (P < 0.05) in trained versus untrained legs, but despite this, arterio-venous extraction glucose did not decrease in trained legs. Thus, leg glucose clearance was increased in trained legs (P < 0.05) and more than explained by increases in muscle mass. Strength training increased protein content of GLUT4, insulin receptor, protein kinase B-␣/, glycogen syn-thase (GS), and GS total activity. In conclusion, we found that strength training for 30 min three times per week increases insulin action in skeletal muscle in both groups. The adaptation is attributable to local contraction mediated mechanisms involving key proteins in the insulin signaling cascade. Diabetes 53:294 –305, 2004 I t is an established finding that aerobic endurance training increases insulin action in patients with type 2 diabetes (1–9), and also that the effect of training is predominantly located to the skeletal muscle (10). Glycemic control also improves along with training (11). Furthermore, with the increased insulin action, the need for insulin to mediate the clearance of a given amount of glucose is lessened. Thus, the need for exogenous insulin or oral hypoglycemic agents is decreased (12). Apart from the beneficial effects on glucose metabolism, physical training also exerts marked improvement on most of the components of the metabolic syndrome (13). Despite the scientific evidence of the therapeutic effect of exercise training, it is a well-known clinical experience that it is often very difficult to engage the patients into taking exercise on a regular basis, and even if one succeeds , the adherence is disappointing. The majority of patients with type 2 diabetes are overweight and have usually been sedentary for the major part of their lives. For many reasons, both psychological and sociological, they are not likely to take up endurance training. Obesity may even be a physical problem in the performance of exercise , especially endurance-type exercises. For patients with type 2 diabetes, resistance training probably represents an attractive exercise modality, but little is known about the overall effect, and the effect in muscle has not been studied. Furthermore, dose-response studies on resistance training effects have not been carried out. To provide support for the recommendations about the type and intensity of effective exercise, we have now carried out a study where we investigated the effect of a very low amount of strength training on insulin action in the skeletal muscle in patients with type 2 diabetes. Based on the sparse literature available on strength training regimens in these patients (14 –19), we used a training program that we a priori considered to be minimally effective. We used a one-legged training protocol, a model that is robust against biological variation and that has previously been used to demonstrate the effect of endurance training on skeletal muscle insulin sensitivity (10). Second, we obtained muscle biopsies from both legs and analyzed these for differences in content and activities of proteins and enzymes that could explain a possible effect of strength training.
... This leads to increased glucose transporters activity and increased insulin sensitivity (Dray et al., 2008). Hence, regular physical activity may increase glucose consumption in cells, especially muscle cells and overcome insulin receptor disorders (Holten et al., 2004; Dray et al., 2008). ...
... kinase, protein kinase B (Akt), glucose transporter (GLUT4), insulin receptor, and insulin receptor substrate 1.2 (Thorell et al., 1999; Lemieux et al., 2000). This finding (Effect of three times a week aerobic exercise and 5 times a week aerobic exercise on insulin receptors level) is consistent with findings of Forsig et al. (2007) and Holten et al. (2004). It is also inconsistent with findings of Christian et al. (2002). ...
... This inconsistency may be due to difference in selected sample; in this study, obese rats were used and we used the diabetic rats. This finding (effect of three times a week aerobic exercise on glucose transporter protein (GLUT4) level) is inconsistent with findings of Zarekar and colleagues (Zarekar et al., 2014), Park et al. (2011), Ross et al. (2009), Holten et al. (2004), Forsig et al. (2007, and Christine et al (2002). This insignificance does not mean that the 3 times a week aerobic exercise have no effect; it indicates that the effect was low. ...
Objectives: The diabetes is a metabolic disease which is caused by chronic disease of blood glucose due to low insulin secretion, insulin resistance, or both of them. The sports activities have a major impact on prevention, treatment, and reduction of diabetes effects. Therefore, this study aimed to review and compare the impact of aerobic exercise (3 and 5 times per week) on some factors which are involved in glucose transition to skeletal muscles of diabetic rats. Materials & Methods: A total of 30 Wistar rats were divided into three groups: diabetic, control (n=8); exercise group, 3 times a week (n=11); and exercise group, 5 times a week (n=11). The exercise groups ran on treadmill for 6 weeks with progressive intensity and duration. The variance analysis test was used to detect the significance of difference between groups. Also, the paired t-test was used to evaluate changes of groups in pre-test and post-test. Results: The findings showed that the insulin sensitivity and insulin receptor levels increased significantly in aerobic exercise groups (3 and 5 times a week) compared to control group (p<0.05). The aerobic exercise (three times a week) did not significantly increase the levels of glucose transporter protein (GLUT4) in exercise group compared to control group. However, aerobic exercise (five times a week) increased significantly the levels of glucose transporter protein (GLUT4) in exercise group compared to control group (p<0.05). Conclusions: The findings showed that aerobic exercise increased insulin receptors levels, glucose transporter proteins (GLUT4), and insulin sensitivity level. Also, the findings showed that the number of exercise session per week may be effective in management of diabetes and reduction of its destructive effects.
... Our study reinforces the importance of regular exercise, as suggested by the current exercise guidelines, and its enhancement of insulin sensitivity. The exercise-induced increase in insulin sensitivity is believed to reflect adaptations in muscle insulin signaling [40,41], GLUT4 protein expression, content and action [6,7] and associated improvement in insulin-stimulated glucose disposal and glycogen synthesis [40,41] . This is accompanied and influenced by enhanced intramyocellular oxidative enzyme capacity and possibly changes in muscle architecture from fast-type to slow-type fibres [42,43]. ...
... Our study reinforces the importance of regular exercise, as suggested by the current exercise guidelines, and its enhancement of insulin sensitivity. The exercise-induced increase in insulin sensitivity is believed to reflect adaptations in muscle insulin signaling [40,41], GLUT4 protein expression, content and action [6,7] and associated improvement in insulin-stimulated glucose disposal and glycogen synthesis [40,41] . This is accompanied and influenced by enhanced intramyocellular oxidative enzyme capacity and possibly changes in muscle architecture from fast-type to slow-type fibres [42,43]. ...
The purpose of this study was to examine the effect of regular exercise training on insulin sensitivity in adults with type 2 diabetes mellitus (T2DM) using the pooled data available from randomised controlled trials. In addition, we sought to determine whether short-term periods of physical inactivity diminish the exercise-induced improvement in insulin sensitivity. Eligible trials included exercise interventions that involved ≥3 exercise sessions, and reported a dynamic measurement of insulin sensitivity. There was a significant pooled effect size (ES) for the effect of exercise on insulin sensitivity (ES, –0.588; 95% confidence interval [CI], –0.816 to –0.359; P<0.001). Of the 14 studies included for meta-analyses, nine studies reported the time of data collection from the last exercise bout. There was a significant improvement in insulin sensitivity in favour of exercise versus control between 48 and 72 hours after exercise (ES, –0.702; 95% CI, –1.392 to –0.012; P=0.046); and this persisted when insulin sensitivity was measured more than 72 hours after the last exercise session (ES, –0.890; 95% CI, –1.675 to –0.105; P=0.026). Regular exercise has a significant benefit on insulin sensitivity in adults with T2DM and this may persist beyond 72 hours after the last exercise session.
... En niños y adolescentes se ha descrito una asociación independiente entre la capacidad muscular y la sensibilidad a la insulina [25] y las concentraciones de proteínas proinflamatorias como PCR y prealbumina [20] . Es conocido que el entrenamiento de fuerza en niños y adultos mejora el perfil in- flamatorio383940, el balance glicémico [41], el metabolismo de las grasas [42], la sensibilidad a la insulina [41][43][44] y la función endotelial [42] tejido adiposo con capacidad endocrina [45] . Así, las citoquinas derivadas del músculo (mioquinas), en particular las producidas en las fibras musculares tipo II [46][47] , promueven un ambiente antiinflamatorio y antiaterogénico a través de efectos sistémicos y/o específicos en la grasa visceral [48]. ...
... En niños y adolescentes se ha descrito una asociación independiente entre la capacidad muscular y la sensibilidad a la insulina [25] y las concentraciones de proteínas proinflamatorias como PCR y prealbumina [20] . Es conocido que el entrenamiento de fuerza en niños y adultos mejora el perfil in- flamatorio383940, el balance glicémico [41], el metabolismo de las grasas [42], la sensibilidad a la insulina [41][43][44] y la función endotelial [42] tejido adiposo con capacidad endocrina [45] . Así, las citoquinas derivadas del músculo (mioquinas), en particular las producidas en las fibras musculares tipo II [46][47] , promueven un ambiente antiinflamatorio y antiaterogénico a través de efectos sistémicos y/o específicos en la grasa visceral [48]. ...
Objective: To examine the association between cardio respiratory and muscular fitness and the presence of obesity and other cardiovascular and metabolic risk factors in school children. Material and method: Cross-sectional study, conducted in 336 school children (boys and girls) in grade 5º and 6º of public schools in the city of Bucaramanga, Colombia. Results: Significant inverse correlations were found between body mass index (BMI) and grip strength adjusted for weight (-0532) (P <0.001), long jump (-0248) (P <0.001) and Yo-Yo test (-0.321) (P <0.001). The maximum grip strength was correlated inversely with systolic blood pressure (SBP) (-0115) (p <0.05). Conclusion: Obesity assessed by BMI and body fat percent is inversely related with muscular and cardiorespiratory fitness in Colombian school children.
... O exercício físico possui efeito hipoglicêmico agudo e crônico em indivíduos diabéticos independente de insulina, estimulando a captação da glicose nos tecidos adiposo e muscular, bem como alterando a sensibilidade a insulina (HOLTEN et al., 2004). Estudos recentes têm evidenciado que no pós-treinamento resistido, aeróbico, combinado (resistido em conjunto ao aeróbico na mesma ou em sessões diferentes) ou treinamento intervalado de alta intensidade (HIIT) é possível manter os valores glicêmicos regulados por até 48 horas em indivíduos diabéticos tipo 2. No entanto, para mantê-los cronicamente, é necessário que haja uma frequência semanal regular dos exercícios prescritos, não devendo ultrapassar intervalos maiores que 72 horas (LLOPIZ, GALBIS, 2015). ...
A hiperglicemia, defeitos na produção/secreção de insulina e resistência a esse hormônio, são características fisiopatológicas observadas em indivíduos diabéticos tipo 2. O exercício físico é um aliado importante para o manejo glicêmico, porém os mecanismos envolvidos nesse processo são múltiplos, complexos e precisam ser mais explorados. O objetivo deste estudo foi analisar os mecanismos moleculares independente de insulina envolvidos no controle glicêmico em diabéticos tipo 2 em resposta ao exercício físico. Trata-se de uma revisão integrativa, com período de busca de 2000 a 2020 de artigos indexados nas bases de dados PubMed, SciELO e Medline, com os descritores encontrados no DECS e MESH. Foram investigados sujeitos diabéticos tipo 2 de ambos os sexos e com idade superior a 18 anos. Foram encontrados 632 artigos, dos quais apenas 4 (n=88) atenderam aos critérios de inclusão. O exercício físico pode auxiliar no manejo glicêmico de diabéticos tipo 2, pois estimula vias através da contração muscular, causando aumento da expressão proteica nos tecidos, com maior destaque para a ativação da 5'-monofosfato-adenosina proteína quinase ativada e do transportador de glicose 4 nos diabéticos insulinorresistentes. Embora as evidências tenham mostrado que a ativação de algu-mas moléculas em resposta ao exercício físico seja benéfica para o manejo glicêmico do diabetes tipo 2, há necessidade de maior exploração desses mecanismos, pois ainda não estão bem descritos na literatura. Palavras-chave: Diabetes tipo 2, GLUT4, Captação, Exercício físico, Quinases. ABSTRACT Hyperglycemia, defects in insulin production/secretion and resistance to this hormone are pathophysiological characteristics observed in type 2 diabetic individuals. Physical exercise is an important ally for glycemic management, but the mechanisms involved in this process are multiple, complex and need to be further explored. The aim of this study was to analyze the independent molecular mechanisms of insulin involved in glycemic control in type 2 diabetics in response to physical exercise. This is an integrative review, with a search period from 2000 to 2020 of articles indexed in the PubMed, SciELO and Medline databases, with the descriptors found in decs and mesh. Type 2 diabetic subjects of both sexes and older than 18 years were investigated. A total of 632 articles were found, of which only 4 (n=88) met the inclusion criteria. Physical exercise can help in the glycemic management of type 2 diabetics, as it stimulates pathways through muscle contraction, causing increased protein expression in tissues, with greater emphasis on the activation of 5'-monophosphate-adenosine activated protein kinase and glucose transporter 4 in insulin-resistant diabetics. Although evidence has shown that the activation of some molecules in response to physical exercise is beneficial for glycemic management of type 2 diabetes, there is a need for greater exploration of these mechanisms, as they are not yet well described in the literature.
... GLUT4 permits facilitated diffusion of glucose into skeletal muscles, and therefore, a larger concentration of GLUT4 and faster movement of GLUT4 to the cell surface with resistance training will enhance glucose flux into the cell, and therefore better regulate blood glucose levels. Resistance training also directly increases the content and rate of GLUT4 translocation within the muscle cell [57]. Importantly, these changes occur independent of significant increases in muscle mass [58], and even after only one resistance training session or single set of exercises [51], suggesting that repeated mechanical muscular contractions, rather than muscle growth, may be the most important for glucose control in T2DM. ...
Gestational diabetes mellitus (GDM) poses a significant threat to the short- and long-term health of the mother and baby. Pharmacological treatments for GDM do not fully correct the underlying problem of the disease; however, non-pharmacological treatments such as exercise are increasingly recognized as foundational to glycemic management in other populations with disordered glucose regulation, such as non-gravid women with type II diabetes mellitus (T2DM). Much of the research regarding the impact of exercise on glycemic control in T2DM leverages aerobic training as the primary modality; yet research has demonstrated the effectiveness of resistance training on improving glycemic control in T2DM. This chapter will review the rationale for resistance training in the management of GDM using evidence from individuals with T2DM; then the chapter will review available studies on the effectiveness of resistance training on glucose control in women with GDM.
... O exercício físico possui efeito hipoglicêmico agudo e crônico em indivíduos diabéticos independente de insulina, estimulando a captação da glicose nos tecidos adiposo e muscular, bem como alterando a sensibilidade a insulina (HOLTEN et al., 2004). Estudos recentes têm evidenciado que no pós-treinamento resistido, aeróbico, combinado (resistido em conjunto ao aeróbico na mesma ou em sessões diferentes) ou treinamento intervalado de alta intensidade (HIIT) é possível manter os valores glicêmicos regulados por até 48 horas em indivíduos diabéticos tipo 2. No entanto, para mantê-los cronicamente, é necessário que haja uma frequência semanal regular dos exercícios prescritos, não devendo ultrapassar intervalos maiores que 72 horas (LLOPIZ, GALBIS, 2015). ...
A hiperglicemia, defeitos na produção/secreção de insulina e resistência a esse hormônio, são características fisiopatológicas observadas em indivíduos diabéticos tipo 2. O exercício físico é um aliado importante para o manejo glicêmico, porém os mecanismos envolvidos nesse processo são múltiplos, complexos e precisam ser
mais explorados. O objetivo deste estudo foi analisar os mecanismos moleculares independente de insulina envolvidos no controle glicêmico em diabéticos tipo 2 em resposta ao exercício físico. Trata-se de uma revisão integrativa, com período de busca de 2000 a 2020 de artigos indexados nas bases de dados PubMed, SciELO e Medline, com os descritores encontrados no DECS e MESH. Foram investigados sujeitos diabéticos tipo 2 de ambos os sexos e com idade superior a 18 anos. Foram encontrados 632 artigos, dos quais apenas 4 (n=88) atenderam aos critérios de inclusão. O exercício físico pode auxiliar no manejo glicêmico de diabéticos tipo 2,
pois estimula vias através da contração muscular, causando aumento da expressão proteica nos tecidos, com maior destaque para a ativação da 5’-monofosfato-adenosina proteína quinase ativada e do transportador de glicose 4 nos diabéticos insulinorresistentes. Embora as evidências tenham mostrado que a ativação de algumas moléculas em resposta ao exercício físico seja benéfica para o manejo glicêmico do diabetes tipo 2, há necessidade de maior exploração desses mecanismos, pois ainda não estão bem descritos na literatura.
... Regular moderate exercise has been suggested to reduce advanced glycation and ameliorate early diabetic nephropathy in obese Zucker rats [27]. Thus it can be concluded that exercise training reduces VEGF upregulation in the diabetic kidney by decreasing the hyperglycemia resulting from the improved glucose uptake due to the increased insulin sensitivity as suggested by previous reports [42][43][44]. ...
Background: Nephropathy is a significant complication of diabetes mellitus, which is associated with high morbidity and mortality. Exercise training has been shown to have renoprotective effects in diabetes. Unregulated vascular endothelial growth factor (VEGF) has been demonstrated in the diabetic kidney. Thus, the aim of our study is to illustrate the impact of endurance exercise training on the renal VEGF expression in type I diabetic rats.
... Because muscle-strengthening activities are strongly related to gains in muscle strength in youth [61,62], these observations support our analysis and suggest that low muscle fitness is causally related to development of unfavorable levels of insulin resistance. A possible mechanism through which high muscular fitness may influence insulin resistance is by stimulating proteins in the insulin-signaling cascade [63]. Consistent with this, several experimental studies support the biological plausibility of our findings, suggesting that increased muscular fitness via resistance training favors increased insulin sensitivity [64]. ...
Background:
No previous systematic review has quantitatively examined the association between muscular fitness during childhood and adolescence and health parameters later in life.
Objective:
The aim was to systematically review and meta-analyze the current evidence for a prospective association between muscular fitness in childhood and adolescence and future health status.
Methods:
Two authors systematically searched MEDLINE, EMBASE and SPORTDiscus electronic databases and conducted manual searching of reference lists of selected articles. Relevant articles were identified by the following criteria: apparently healthy children and adolescents aged 3-18 years with muscular fitness assessed at baseline (e.g., handgrip, standing long jump, sit-ups, among others), and a follow-up period of ≥ 1 year. The outcome measures were anthropometric and adiposity measurements and cardiometabolic, bone and musculoskeletal health parameters. Two authors independently extracted data.
Results:
Thirty studies were included in the meta-analysis, yielding a total of 21,686 participants. The meta-analysis found a significant, moderate-large (p < 0.05) effect size between muscular fitness at baseline and body mass index (r = - 0.14; 95% confidence interval (CI) - 0.21 to - 0.07), skinfold thickness (r = - 0.32; 95% CI - 0.40 to - 0.23), homeostasis model assessment estimated insulin resistance (r = - 0.10; 95% CI - 0.16 to - 0.05), triglycerides (r = - 0.22; 95% CI - 0.30 to - 0.13), cardiovascular disease risk score (r = - 0.29; 95% CI - 0.39 to - 0.18), and bone mineral density (r = 0.166; 95% CI 0.086 to 0.243) at follow-up.
Conclusion:
A prospective negative association was observed between muscular fitness in childhood/adolescence and adiposity and cardiometabolic parameters in later life, together with a positive association for bone health. There is inconclusive evidence for low back pain benefits.
... The results of the studies included in the present review indicated the absence of relationship between MF and FG in children and adolescents. Studies with adults have identified a better blood glucose profile in individuals with higher MF (20,43). Although clinical symptoms associated with CVDs typically tend to manifest during adulthood, the genesis of CVD risk factors begins during childhood (28). ...
Rodrigues de Lima, T, Custódio Martins, P, Henrique Guerra, P, and Augusto Santos Silva, D. Muscular fitness and cardiovascular risk factors in children and adolescents: A systematic review. J Strength Cond Res XX(X): 000-000, 2018-The purpose of this study was to identify and summarize the relationships between muscular fitness (MF) and individual components of metabolic syndrome (high waist circumference [WC], high blood pressure [BP], high systolic BP [SBP], high diastolic BP [DBP], high triglycerides [TG], fasting blood glucose [FG], and low HDL cholesterol levels [HDL-C]) in children and adolescents. A systematic review was conducted in 5 electronic databases, with complementary searches in reference lists, and the inclusion criteria were children and adolescents (age group up to 19 years of age) with no special clinical conditions. In all articles, risk of bias was analyzed by a standardized instrument. Of the 5,973 articles initially identified, 21 were included, with data on 22,261 children and adolescents. Higher MF values were associated with lower TG (n = 07) and WC values (n = 15). Different results in relation to the relationship between MF and SBP (n = 10) and MF and DBP (n = 07) were verified. In addition, there was no relationship between MF and FG (n = 06). In addition, inconclusive results were verified in the relationship between MF and HDL-C (n = 07). Concluded higher MF values were related to lower WC values and lower TG concentrations.
... Many benefits of REX have been reported in T2DM patients. In addition, to decreasing neuropathy and pain, REX improved the glycemic index, HbA1C, adiposity and muscle strength [145,173,174], it also reduced fasting insulin, increased insulin sensitivity, glucose disposal rates and improved glucose tolerance [175][176][177][178][179]. REX increased glucose uptake in muscles by increasing and translocating GLUT4 to the plasma membrane [180] . ...
Diabetes has been on the rise globally. Although many factors contribute to the increasing risk and manifestation of this disease lack and decreased physical activity/ exercise stands out as one of the major factors. Treatment interventions for prediabetic and diabetic patients include diet and lifestyle changes with enhanced physical activity/ exercise. Several types of physical activity are available for these patients but, recommendations have to be made on an individual basis after giving due consideration to the co morbidities and other risks and barriers. Implementation of progressive resistance therapy may be successful in maintaining glucose homeostasis in diabetic patients.
... Though training intensity and the time point of investigation appear to be important for exercise-induced activation of insulin signaling, there is still a lack of knowledge about the underlying mechanisms of acute exercise and effects of different training factors, such as modality and intensity, on insulin signaling. Chronic exercise can also lead to higher rates of tyrosine phosphorylation of key molecules in the insulin signaling cascade in muscle of healthy as well as insulin-resistant individuals [52, 95, 96]. A recent exercise study observed enhanced whole-body insulin action and increased Akt and AS160 phosphorylation after 10 weeks of chronic resistance training with exercises for upper and lower body and running endurance training in untrained individuals [52] indicating an independence of exercise modality. ...
Insulin resistance plays a key role in the development of type 2 diabetes. It arises from a combination of genetic predisposition and environmental and lifestyle factors including lack of physical exercise and poor nutrition habits. The increased risk of type 2 diabetes is molecularly based on defects in insulin signaling, insulin secretion, and inflammation. The present review aims to give an overview on the molecular mechanisms underlying the uptake of glucose and related signaling pathways after acute and chronic exercise. Physical exercise, as crucial part in the prevention and treatment of diabetes, has marked acute and chronic effects on glucose disposal and related inflammatory signaling pathways. Exercise can stimulate molecular signaling pathways leading to glucose transport into the cell. Furthermore, physical exercise has the potential to modulate inflammatory processes by affecting specific inflammatory signaling pathways which can interfere with signaling pathways of the glucose uptake. The intensity of physical training appears to be the primary determinant of the degree of metabolic improvement modulating the molecular signaling pathways in a dose-response pattern, whereas training modality seems to have a secondary role.
... Resistance training has been found to be effective for managing T2DM patients and may provide additional benefits for preventing or limiting muscular dysfunction related with T2DM [1][2][3][4]16]. Additionally, resistance training increases the protein contents of GLUT4, insulin receptor, glycogen synthase (GS) and GS total activity [17]. In our previous animal study, the expression of GLUT4 protein was increased in skeletal muscles using the same protocol as the present study, with high-intensity progressive resistance training using a ladder and tail weights (our unpublished data). ...
Purpose:
In the present study, we investigated the effects of 8 weeks of progressive resistance training on the level of skeletal muscle derived BDNF as well as glucose intolerance in Zucker diabetic rats.
Methods:
Six week-old male Zucker diabetic fatty (ZDF) and Zucker lean control (ZLC) rats were randomly divided into 3 groups: sedentary ZLC (ZLC-Con), sedentary ZDF (ZDF-Con), and exercised ZDF (ZDF-Ex). Progressive resistance training using a ladder and tail weights was performed for 8 weeks (3 days/week).
Results:
After 8 weeks of resistance training, substantial reduction in body weight was observed in ZDF-Ex compared to ZDF-Con. Though the skeletal muscle volume did not change, grip strength grip strength was significantly higher in ZDF-Ex compared to ZDF-Con. In the soleus, the level of BDNF was increased in ZDF-Con, but was significantly decreased (p<0.05) in ZDF-Ex, showing a training effect. Moreover, we found that there was a negative correlation (r=-0.657; p=0.004) between grip strength and BDNF level whereas there was a positive correlation (r=0.612; p=0.008) between plasma glucose level and BDNF level in skeletal muscle.
Conclusion:
Based upon our results, we demonstrated that resistance training inhibited the elevation of skeletal muscle derived-BDNF expression concomitant with the improvement of muscle strength in zucker diabetic rats. In addition, muscle-derived BDNF might be a potential mediator for the preventive effect of resistance training on the progress of type 2 diabetes.
... This, in turn, leads to disease exacerbation for creating a vicious cycle in which the high intrahepatic lipid concentration inhibits insulin action in the liver, leading to high portal levels of insulin and increase in intrahepatic lipids [84]. There is data suggesting that physical exercise (both aerobics and resistance) may break this cycle by improving glucose control and lipid oxidation through augmentation of GLUT-4 glucose transporter in striate muscle, expression and activity of glycogen synthase enzyme, insulin receptors, and glycogen storage in muscle and liver [81, 85]. Therefore, resistance exercise seems to have a beneficial effect on NAFLD by enhancing circulating FA and glucose uptake, thus reducing the impact of hepatic insulin-stimulated de novo lipogenesis. ...
Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and it is associated with other medical conditions such as diabetes mellitus, metabolic syndrome, and obesity. The mechanisms of the underlying disease development and progression are not completely established and there is no consensus concerning the pharmacological treatment. In the gold standard treatment for NAFLD weight loss, dietary therapy, and physical activity are included. However, little scientific evidence is available on diet and/or physical activity and NAFLD specifically. Many dietary approaches such as Mediterranean and DASH diet are used for treatment of other cardiometabolic risk factors such as insulin resistance and type-2 diabetes mellitus (T2DM), but on the basis of its components their role in NAFLD has been discussed. In this review, the implications of current dietary and exercise approaches, including Brazilian and other guidelines, are discussed, with a focus on determining the optimal nonpharmacological treatment to prescribe for NAFLD.
... The observed reductions in HbA1c levels in the PRT group in this study may have resulted from mechanisms involving increasing levels of muscle GLUT4, insulin receptors, protein kinase B, glycogen synthase and glycogen synthase total activity following PRT. Previous research has found that strength training for 30 minutes three times per week increases insulin action in skeletal muscle by the said mechanisms. [21] Upper body and lower body muscular strength gains in the PRT group may have led to increased insulin action in skeletal muscle, an effect that may be attributed to qualitative muscular adaptations to resistance training. ...
Resistance Training Leads to Clinically Meaningful
Improvements in Control of Glycemia and Muscular
Strength in Untrained Middle-aged Patients
with type 2 Diabetes Mellitus
... The benefits of exercise training for counteracting the detrimental effect of diabetes 18 on both glyco-metabolic control and neuromuscular function have been well reported. 19 Resistance training in particular has been seen to improve both muscle strength and 20 mass as well as insulin sensitivity (Brooks et al., 2007; Cauza et al., 2005; Dunstan et 21 al., 2002; Holten et al., 2004; LeBrasseur et al., 2011; Mann et al., 2014). For these 22 reasons, it may be desirable that type 2 diabetes patients would begin an appropriate 23 exercise training program as soon as possible after diagnosis to prevent, or at least 24 limit, the decline in neuromuscular function. ...
The effects of exercise training on neuromuscular function of arm and leg muscles in type 2 diabetic patients (T2D) was investigated.
Eight T2D sedentary male patients (61.0±2.3years) and eight sedentary healthy age matched control subjects (H, 63.9±3.8years) underwent a 16-week supervised combined endurance and resistance exercise program. Before and after training, maximal isometric (MVIC), isokinetic (15, 30, 60, 120, 180, 240°s(-1)) torque and muscle endurance of the elbow flexors (EF) and knee extensors (KE) were assessed. Simultaneously, surface electromyographic signals from biceps brachii (BB) and vastus lateralis (VL) muscles were recorded and muscle fiber conduction velocity (MFCV) estimated.
Following training, maximal torque of the KE increased during MVIC and isokinetic contractions at 15 and 30°s(-1) in the T2D (+19.1±2.7% on average; p<0.05) but not in the H group (+7±0.9%; p>0.05). MFCV recorded from the VL during MVIC and during isokinetic contractions at 15 and 30°s(-1) increased (+11.2±1.6% on average; p<0.01), but in the diabetic group only. Muscular endurance was lower in T2D (20.1±0.7s) compared to H (26.9±1.3s), with an associated increase in the MFCV slope after training in the KE muscles only.
The effect of a combined exercise training on muscle torque appears to be angular velocity-specific in diabetic individuals, with a more pronounced effect on KE muscles and at slow contraction velocities, along with an associated increase in the MFCV. MFCV appears to be a more sensitive marker than torque in detecting the early signs of neuromuscular function reconditioning.
Copyright © 2015 Elsevier Ltd. All rights reserved.
... xercise done for six months improved insulin sensitivity even without significant changes on BMI of the obese participants. Skeletal muscle is known to play a major role in the elimination of glucose from circulation. Approximately 85% of the whole body glucose disposal in the fed state is attributed to skeletal muscle (DeFronzo & Ferrannini 1991). Holten et al. (2004) reported a novel finding where an increase in insulin action in skeletal muscle was not solely caused by the increase of muscle mass. They reported a significant increase in protein content involved in the insulin signalling cascade. The proteins were GLUT4, protein kinase B-α/β and glycogen synthase. The present study was not able to y ...
Obesity is characterised by an excessive amount of body fat accumulation which leads to multiple chronic diseases. Bodies of evidence showed physical activity (PA) plays an important role in the management of obesity. The aim of this study to measure the effect of High Intensity Circuit Training (HICT) on body composition, cardiovascular risk factors, and physical fitness among overweight and obese female students. Participants were recruited among students of the Faculty of Health Science, UKM. They were assigned into intervention and control group with. The intervention group (n = 10) underwent HICT, thrice weekly for 12 weeks. While control (n = 10) were asked continue their daily routine without any changes. Body body composition, (BMI, fat percentage, fat and muscle mass), biochemical parameters (Glucose, Total Cholesterol, Triglyceride, Blood Pressure) and physical fitness (cardiorespiratory, muscle strength and agility) were assessed at baseline and after 12 weeks training. Independent T-test was used to compare parameters at baseline and mixed ANOVA was used to analyse the effect of the intervention at the end of study period. The significant level was set at p < 0.05. Body weight and composition revealed no significant difference between group and no interaction between time and group. Total cholesterol triglycerides, systolic BP and diastolic BP also showed no significant difference between group and interaction between time and group. However, the blood glucose level showed significant interaction between time and group after 12 weeks of HICT (F(1,16) = 12.63, p < 0.05). Meanwhile physical fitness showed significant improvement for VO 2max F(1,18) = 6.43, p < 0.05 and F(1,18) = 6.94, p < 0.05 for both between group and interaction between time and group. The hand grip test showed significant difference F(1, 18) = 1.58, p < 0.05 between the group but no interaction between time and group after 12-week exercise training. Agility test also showed no significant difference in both between group and time-group interaction after the end of 12 week HICT. In conclusion, this study showed that High Intensity Circuit Training can significantly improve the blood glucose level, VO 2max and muscle strength of the participants, however, revealed no significant changes to other parameters.
... The mechanism of increased glycemic control with Volume 6 @BULLET Issue 5 @BULLET 1000539 J DDaaeees Meeaa ISSN: 2155-6156 JDM, an open access journal this intervention may relate to GLUT4 signaling. GLUT4 density has been shown to increase by 40% with high intensity resistance training [36]. Resistance exercise that is associated with fatigue of the structure of the muscle cell, as opposed to fatigue associated with ATP stores, has a myofibril protein syntheses (MPS) implication [37]. ...
Type 2 diabetes is a systemic, multifactorial disease that is a leading cause of morbidity and mortality globally. Despite a rise in the number of available medications and treatments available for management, exercise remains a first-line prevention and intervention strategy due to established safety, efficacy, and tolerability in the general population. Herein we review the predisposing risk factors for, prevention, pathophysiology, and treatment of type 2 diabetes. We emphasize key cellular and molecular adaptive processes that provide insight into our evolving understanding of how, when, and what types of exercise may improve glycemic control. © 2023 American Physiological Society. Compr Physiol 13:1-27, 2023.
Although physical activity is widely recommended for preventing and treating cardiovascular complications of type 2 diabetes mellitus (T2DM), the underlying mechanisms remain unknown. MicroRNA-126 (miR-126) is an angiogenetic regulator abundant in endothelial cells (ECs) and endothelial progenitor cells (EPCs). It is primarily involved in angiogenesis, inflammation and apoptosis for cardiovascular protection. According to recent studies, the levels of miR-126 in the myocardium and circulation are affected by exercise protocol. High-intensity interval training (HIIT) or moderate-and high-intensity aerobic exercise, whether acute or chronic, can increase circulating miR-126 in healthy adults. Chronic aerobic exercise can effectively rescue the reduction of myocardial and circulating miR-126 and vascular endothelial growth factor (VEGF) in diabetic mice against diabetic vascular injury. Resistance exercise can raise circulating VEGF levels, but it may have a little influence on circulating miR-126. The Several targets of miR-126 have been suggested for cardiovascular fitness, such as sprouty-related EVH1 domain-containing protein 1 (SPRED1), phosphoinositide-3-kinase regulatory subunit 2 (PIK3R2), vascular cell adhesion molecule 1 (VCAM1), high-mobility group box 1 (HMGB1), and tumor necrosis factor receptor-associated factor 7 (TRAF7). Here, we present a comprehensive review of the roles of miR-126 and its downstream proteins as exercise mechanisms, and propose that miR-126 can be applied as an exercise indicator for cardiovascular prescriptions and as a preventive or therapeutic target for cardiovascular complications in T2DM.
Type 2 diabetes (T2D) is associated with chronic inflammation as a critical factor for muscle atrophy and disease progression. Although the combination of aerobic and resistance training leads to more significant improvements in health-related indices for T2D patients, the interference effect in concurrent training can decrease positive adaptations. The purpose of this study was to investigate the physiological adaptations in performing high-intensity interval training (HIIT) and resistance training on the same day vs. different days in T2D patients. Twenty-four non-athletic 45–65-year-old women with T2D participated in an 8-week intervention. They were randomly divided into three groups: same days (SD), different days (DD), and treatment as usual (control). SD group had resistance training followed by HIIT on Saturday, Monday, and Wednesday. In contrast, the DD group had the same volume of resistance training on Saturday, Monday, and Wednesday and HIIT on Sunday, Tuesday, and Thursday, with Friday as a resting day. Blood samples were collected 24 h before the first and 48 h after the last session in each group to measure glucose, insulin, glycosylated hemoglobin, IGF1, IL1β, CRP, lipid profile, miR-146a, and miR-29b. Three subjects dropped out during the study, and 21 participants (SD = 7, DD = 6, Control = 8) completed the 8-week intervention. MiR-146a changed significantly (P = 0.006) in both SD and DD groups compared to the control group. IGF1 (P = 0.001) and fat-free mass (P = 0.001) changed significantly in SD and DD groups compared to the control group, and also DD led to more significant increases in IGF1 and fat-free mass in comparison with SD. MiR-29 (P = 0.001) changed significantly in the DD group compared to the control group. The reduction of IL-1β, fat mass and insulin resistance was significant in SD and DD compared to the control group; DD showed more potent effects than the SD group on the fat mass (P = 0.001) and insulin resistance (P = 0.001). This study demonstrated that a combination of HIIT and resistance training could be practical for improving health-related outcomes in T2D. Our study indicated for the first time that training strength and HIIT on separate days appeared to be more effective to combat muscle atrophy and insulin resistance.
Physical activity is a fundamental therapeutic aid in the management of type 2 diabetes (T2D). Regular engagement elicits a plethora of adaptations which leads to improvements in clinical outcomes, such as HbA1c, lipids and blood pressure as well as whole body health and physical function benefits. Those with T2D are encouraged to engage in a minimum of 150 minutes/week of moderate‐intensity physical activity (or 75 minutes/week of vigorous activity). Current recommendations also suggest that this should be supplemented with two‐to‐three resistance, flexibility and/or balance training sessions/week. The latter is particularly encouraged for older individuals or those with limited mobility/poor physical function. Those with T2D are also encouraged to break up prolonged bouts of sitting. However, a large proportion of the general population do not meet current physical activity guidelines, with the figure even lower in those with T2D. Getting started and sustaining a physically active lifestyle is challenging. Therefore, this article aims to provide health care professionals with the information required to tailor guidance to individuals with T2D by: presenting an overview of current guidelines, terminology and benefits; discussing the risk of adverse events; precautions when exercising with complications; practical options for getting started and how to tailor advice in primary care. Where appropriate, individual preferences and motivations should inform decision making regarding exercise modality in order to maximise compliance. That said, the overarching message is that any physical activity is better that none, but more is better especially when combined with a reduction in sitting. Copyright
Chronic muscle loading (overload) induces skeletal muscles to undergo hypertrophy and to increase glucose uptake. Although AMP‐activated protein kinase (AMPK) reportedly serves as a negative regulator of hypertrophy and a positive regulator of glucose uptake, its role in overload‐induced skeletal muscle hypertrophy and glucose uptake is unclear. This study aimed to determine whether AMPK regulates overload‐induced hypertrophy and glucose uptake in skeletal muscles. To this end, skeletal muscle overload was induced through unilateral synergist ablations in wild‐type (WT) and transgenic mice, expressing the dominant‐negative mutation of AMPK (AMPK‐DN). After 14 days, parameters, including muscle fiber cross‐sectional area (CSA), glycogen level, and in vivo [3H]‐2‐deoxy‐D‐glucose uptake, were assessed. No significant difference was observed in body weight or blood glucose level between the WT and AMPK‐DN mice. However, the 14‐day muscle overload activated the AMPK pathway in WT mice skeletal muscle, whereas this response was impaired in the AMPK‐DN mice. Despite a normal CSA gain in each fiber type, the AMPK‐DN mice demonstrated a significant impairment of overload‐induced muscle glucose uptake and glycogenesis, compared to WT mice. Moreover, 14‐day overload‐induced changes in GLUT4 and HKII expression levels were reduced in AMPK‐DN mice, compared to WT mice. This study demonstrated that AMPK activation is indispensable for overload‐induced muscle glucose uptake and glycogenesis; however, it is dispensable for the induction of hypertrophy in AMPK‐DN mice. Furthermore, the AMPK/GLUT4 and HKII axes may regulate overload‐induced muscle glucose uptake and glycogenesis.
Blood flow restriction resistance training (BFRT) employs partial vascular occlusion of exercising muscles via inflation cuffs. Compared with high-load resistance training, mechanical load is markedly reduced with BFRT, but induces similar gains in muscle mass and strength. BFRT is thus an effective training strategy for people with physical limitations. Recent research indicates that BFRT has beneficial effects on glucose and mitochondrial metabolism. BFRT may therefore qualify as a valuable exercise alternative for individuals with type 2 diabetes (T2D), a disorder characterized by impaired glucose metabolism, musculoskeletal decline, and exacerbated progression of sarcopenia. This review covers the effects of BFRT in healthy populations and in persons with impaired physical fitness, the mechanisms of action of this novel training modality, and possible applications for individuals with T2D.
Metabolism is a chain of chemical reactions that are connected in a sequence of pathways. Thus, the sum of an organism’s chemical reactions is called metabolism. It is a harmonizing act among molecular building reactions and degradation of molecules in the body. Therefore, the chemical reactions of living are planned through metabolic pathways. A specific molecule is transformed into a specific molecule, with a specific enzyme that catalyzes each step of the metabolic pathway. The capacity to perform work (biomass energy) is the study of how organisms manage their energy resources. Energy exists in numerous forms, and cells transform chemical energy into mechanical one; body motion, pumping of substances across membranes, and driving chemical reaction in which the standard change in free energy is positive, and energy is absorbed. In cells, critical molecules are either built by connecting small units such as amino acids or nucleotides or degraded into smaller components. Respectively, the reactions responsible for this are referred to as anabolic and catabolic. These reactions consume or yield energy usually in the form of a molecule called adenosine triphosphate. These two progressions compose cell metabolism. Cellular respiration is a catabolic process, the main pathway of catabolism, where it releases energy by degrading complex molecules to smaller composites, such as energy released from glucose breakdown, and is stored in the adenosine triphosphate molecule to release later, the released energy is used in the cell for anabolic pathways. Photosynthesis is an anabolic process done by plants that use energy from sunlight to build complex molecules from smaller composites, sugar, as an example, is formed by the reaction of carbon dioxide gas with water. Thus, all the anabolic processes need additional energy to build different molecules. Some of the glucose produced by the planet is used by the plant itself or is used as a nutrient source by other organisms.
Background
Although low child and adult grip strength is associated with adverse cardiometabolic health, how grip strength across the life course associates with type 2 diabetes is unknown. This study identified the relative contribution of grip strength measured at specific life stages (childhood, young adulthood, mid-adulthood) with prediabetes or type 2 diabetes in mid-adulthood.Methods
Between 1985 and 2019, 263 participants had their grip strength measured using an isometric dynamometer in childhood (9–15 years), young adulthood (28–36 years) and mid-adulthood (38–49 years). In mid-adulthood, a fasting blood sample was collected and tested for glucose and glycated haemoglobin (HbA1c). Participants were categorized as having prediabetes or type 2 diabetes if fasting glucose levels were ≥ 5.6 mmol or if HbA1c levels were ≥ 5.7% (≥ 39 mmol/mol). A Bayesian relevant life course exposure model examined the association between lifelong grip strength and prediabetes or type 2 diabetes.ResultsGrip strength at each time point was equally associated with prediabetes or type 2 diabetes in mid-adulthood (childhood: 37%, young adulthood: 36%, mid-adulthood: 28%). A one standard deviation increase in cumulative grip strength was associated with 34% reduced odds of prediabetes or type 2 diabetes in mid-adulthood (OR 0.66, 95% credible interval 0.40, 0.98).Conclusions
Greater grip strength across the life course could protect against the development of prediabetes and type 2 diabetes. Strategies aimed at increasing muscular strength in childhood and maintaining behaviours to improve strength into adulthood could improve future cardiometabolic health.Video abstract
The Association Between Grip Strength Measured in Childhood, Young- and Mid-adulthood and Prediabetes or Type 2 Diabetes in Mid-adulthood
A four-dimensional model was built to mimic the cross-talk among plasma glucose, plasma insulin, intracellular glucose and cytoplasmic calcium of a cardiomyocyte. A time delay was considered to represent the time required for performing various cellular mechanisms between activation of insulin receptor and subsequent glucose entry from extracellular region into intracellular region of a cardiac cell. We analysed the delay-induced model and deciphered conditions for stability and bifurcation. Extensive numerical computations were performed to validate the analytical results and give further insights. Sensitivity study of the system parameters using LHS-PRCC method reveals that some rate parameters, which represent the input of plasma glucose, absorption of glucose by noncardiac cells and insulin production, are sensitive and may cause significant change in the system dynamics. It was observed that the time taken for transportation of extracellular glucose into the cell through GLUT4 plays an important role in maintaining physiological oscillations of the state variables. Parameter recalibration exercise showed that reduced input rate of glucose in the blood plasma or an alteration in transportation delay may be used for therapeutic targets in diabetic-like condition for maintaining normal cardiac function.
New findings:
What is the central question of this study? Low dose carbon monoxide (CO) inhalation plays a role in regulating proteins involved in glucose metabolism; does low dose CO improve glucose and insulin responses to an oral glucose tolerance test in overweight adults? What is the main finding and its importance? Five days of intermittent CO inhalation does not alter the glucose or insulin responses to ingestion of a glucose bolus in overweight adults. Low dose CO is utilized in various physiological assessment procedures; these findings allow researchers and clinicians to utilize these procedures without concern of altering glucose metabolism.
Abstract:
Low dose carbon monoxide (CO) inhalation upregulates several proteins important for glucose metabolism. Such changes could be clinically significant and may be relevant to those who use CO as a research tool. We hypothesized that low dose CO inhalation would improve glucose and insulin responses to an oral glucose bolus in overweight humans. Eleven young adults (5 men, 6 women; body mass index: 25-35 kg/m2 ) were included in this randomized, placebo-controlled, single-blinded crossover study. Following screening, participants completed two 7-day protocols with a 4-week washout. 24-hours prior to and following 5 consecutive days of either once daily CO (men: 1.2 mL*kg-1 body mass; women: 1.0 mL*kg-1 body mass) or placebo (room air) inhalation, participants underwent oral glucose tolerance tests (OGTT). For key outcome variables, there were no significant main effects or interactions across condition or timepoint (mean ± sd), including fasting glucose (pre-placebo: 85.2 ± 10.1; post-placebo: 82.9 ± 10.6; pre-CO: 83.6 ± 7.7; post-CO: 84.0 ± 9.0 mg/dL), two-hour post glucose (pre-placebo: 100.9 ± 20.0; post-placebo: 98.7 ± 13.1; pre-CO: 94.2 ± 23.2; post-CO: 94.4 ± 14.9 mg/dL), or the Matsuda Index (pre-placebo: 16.1 ± 11.5; post-placebo: 20.3 ± 24.7; pre-CO: 15.6 ± 15.3; post-CO: 17.5 ± 16.8). In conclusion, 5 days of low dose CO administration did not influence glucose and insulin responses to an OGTT in overweight adults. Low dose CO inhalation is utilized in a variety of physiological assessment procedures; these findings allow researchers to utilize these procedures without concern of altering glucose metabolism. This article is protected by copyright. All rights reserved.
This study aimed to assess whether the longitudinal association between childhood muscular fitness and adult measures of glucose homeostasis persist despite changes in muscular fitness across the life course. This prospective longitudinal study included 586 participants who had their muscular power (standing long jump distance), cardiorespiratory fitness (CRF) and waist circumference measured as children (aged 9, 12, 15 years) and again 20 years later as adults. In adulthood, these participants also provided a fasting blood sample which was tested for glucose and insulin. Glucose homeostasis measures including insulin resistance (HOMA2‐IR) and beta cell function (HOMA2‐β) were estimated. Child and adult muscular power levels were separated into thirds and tracking groups (persistently low, decreasing, persistently moderate, increasing, persistently high) were created. Sex‐stratified multivariable linear regression models were used to examine the association between muscular power tracking groups and adult measures of glucose homeostasis. Compared with males with persistently high muscular power, males with increasing and persistently low muscular power had higher fasting insulin (increasing: β=1.12 mU/L, p=0.04; persistently low: β=2.12 mU/L, p=0.001) and HOMA2‐β (increasing: β=8.50%, p=0.03; persistently low: β=11.27%, p=0.01) independent of CRF and males with persistently low muscular power had greater fasting insulin (β=1.22 mU/L, p=0.02) and HOMA2‐IR (β=0.14, p=0.02) independent of waist circumference. Non‐significant associations were present for females. For males, maintaining persistently high muscular power between childhood and adulthood could lead to a healthier adult glucose homeostasis profile.
Objectives. Diabetes mellitus is associated with dyslipidemia, which contributes to a higher risk of thrombosis, atherosclerosis and cardiovascular disease. This study evaluated the effects of leucine and resistance training on the serum lipid profile in rats with streptozotocin-induced diabetes for 8 weeks.
Methods. Wistar rats with neonatal streptozotocin-induced diabetes were treated with leucine supplementation (5%) and/or resistance training (3 days per week) for 8 weeks, and divided in DL (diabetic and leucine), DT (diabetic and resistance training group) and DLT (diabetic, leucine and resistance training) groups. Others 2 groups of animals received isonitrogen AIN-93M diet that was defined as a control diet: group D (diabetic untreated) and group C (non-diabetic).
Results. The decrease in serum total cholesterol and increase in high-density lipoprotein cholesterol (HDL-C) was observed in the resistance training-induced diabetic rats when compared with diabetic rats. There was no change in serum lipid profile in leucine-supplemented diabetic rats and no synergistic effect of leucine and resistance training. The fasting glucose levels were reduced in all animals treated compared to D group.
Conclusion. The diabetic trained rats demonstrate a protective effect of resistance training on the serum lipid profile.
Background: Apelin is a novel adipokine that is closely related with insulin resistance and type 2 diabetes. The purpose of the study was to determine the effects of progressive resistance training on plasma concentrations of plasma apelin and insulin resistance in middle-aged men with type 2 diabetes.
Methods: twenty seven types 2 diabetic men selected as subjects and were randomly assigned into two exercise (n=15 aged 46.40 ± 3.02 yrs) and control (n=12 aged 45.06 ± 3.86 yrs) groups. Resistance exercise training was done for 8 weeks (3 days/week, intensity: 30- 70% 1RM) for experimental group. Before and after exercise plasma apelin level, insulin, glucose and insulin resistance (HOMA-IR) after a 12-h fasting was measured. Following the second blood sampling, data analysis was performed and p<0.05 was considered significant. Results: Finding showed that plasma apelin, insulin levels, HOMA-IR, fasting blood glucose (FBG) have significant changes in the exercise group compared to pre-exercise and control groups (p≤0.05).
Conclusion: It seems that low to moderate intensity resistance exercise training has significant effect on the amount of plasma apelin and insulin resistance in type 2 diabetic men. Apelin level may be effective to improve insulin resistance and glycemic control in type 2 diabetic men.
In subjects with frailty syndrome, aging-related loss of muscle (sarcopenia) might progress to the extent that an older person loses his or her ability to live independently. Metabolic syndrome is a set of risk factors (abdominal obesity, insulin resistance, hypertension, and dyslipidemia) which markedly increases the risk of arteriosclerotic vascular disease. Due to the ongoing obesity pandemic and growing elderly population, frailty and metabolic syndromes are major emerging concerns in the healthcare system. Recent studies show that resistance training has remarkable beneficial effects on the musculoskeletal system including the prevention and treatment of these syndromes. Resistance training is probably the most effective measure to prevent and treat sarcopenia. With regard to the effect of resistance training on the muscular strength of elderly persons, the rate of improvement increases with intensity. Resistance training also has a favorable effect on metabolic syndrome since it decreases fat mass including abdominal fat, enhances insulin sensitivity, improves glucose tolerance, and reduces blood pressure values. Optimal nutrition enhances the anabolic effect of resistance training. Resistance training should be a central component of public health promotion programs along with aerobic exercise.
As the blood pressure (BP) and heart rate (HR) response during the recovery period can be influenced by size of activated muscle mass, it is possible that this variable also has some distinct effects on post-exercise rate pressure product (RPP). The aim of the present study was to investigate and compare the systolic (SBP) and diastolic blood pressure (DBP), HR, and RPP responses during recovery to resistance exercise with different body regions. Twelve normotensive young men randomly performed three resistance exercise trials with upper limbs (UL), lower limbs (LL), and whole body (WB), and a control session (CON). All exercise trails included 3 sets of 10 repetitions, with 65% of 1-repetition maximum (1RM) with 2 min rest interval between sets and exercises. SBP, DBP, HR, and RPP were measured before and at each 15 min after exercise until 60 min. Blood lactate (bLAC) was also measured before, and at the 1st minute after the end of exercise. Analysis of variance (ANOVA) and Bonferroni post hoc were used to analyze the data, with a p < .05. The SBP decrease for 60 min after UL, LL, and WB exercise trials was similar, whereas there was no change in post-exercise DBP after the trials. Significant increases were observed in RPP for 15 min after LL, and 30 min after UL and WB. The blood lactate concentration significantly increased after UL, LL and WB resistance exercise when compared to the rest values, as well as in the CON sessions. UL, LL and WB resistance exercise lead to post-exercise hypotension, similar in magnitude and duration, and almost produce the same cardiovascular responses, despite different muscle mass involvement.
Aims
It is unclear whether the potential benefits of physical activity differ according to level of cardiorespiratory fitness (CRF) or strength. The aim of this study was to determine whether the association between physical activity and mortality is moderated by CRF and grip strength sufficiently to inform health promotion strategies.
Methods and results
498 135 participants (54.7% women) from the UK Biobank were included (CRF data available in 67 702 participants). Exposure variables were grip strength, CRF, and physical activity. All-cause mortality and cardiovascular disease (CVD) events were the outcomes. 8591 died over median 4.9 years [IQR 4.3–5.5] follow-up. There was a significant interaction between total physical activity and grip strength (P < 0.0001) whereby the higher hazard of mortality associated with lower physical activity was greatest among participants in the lowest tertile for grip strength (hazard ratio, HR:1.11 [95% CI 1.09–1.14]) and lowest among those in the highest grip strength tertile (HR:1.04 [1.01–1.08]). The interaction with CRF did not reach statistical significance but the pattern was similar. The association between physical activity and mortality was larger among those in the lowest tertile of CRF (HR:1.13 [1.02–1.26]) than those in the highest (HR:1.03 [0.91–1.16]). The pattern for CVD events was similar.
Conclusions
These data provide novel evidence that strength, and possibly CRF, moderate the association between physical activity and mortality. The association between physical activity and mortality is strongest in those with the lowest strength (which is easily measured), and the lowest CRF, suggesting that these sub-groups could benefit most from interventions to increase physical activity.
Interactions between diet, physical activity and genetic predisposition contribute to variable body mass changes observed in response to weight loss interventions. Circulating microRNAs (c-miRNAs) may act as 'biomarkers' that are associated with the rate of change in weight loss, and/or play a role in regulating the biological variation, in response to energy restriction.To quantify targeted c-miRNAs with putative roles in energy metabolism and exercise adaptations following a 16 wk diet and exercise intervention in individuals with large (high responders; HiRes) versus small (low responders; LoRes) losses in body mass.From 89 male and female overweight/obese participants who completed the intervention (energy restriction from diet, 250 kcal/d, and exercise, 250 kcal/d), subgroups of HiRes (>10% body mass loss, n = 22) and LoRes (
The type 1 diabetes patient balances between hyper- and hypoglycemia, and exercise renders diabetes regulation difficult by accelerating the rate of development of these unpleasant alternatives. Based on experience and frequent blood glucose measurements, the insulin dosage must be adjusted to intensity and duration of exercise and food intake. However, well-informed diabetic patients may perform all kinds of sports and even become world champions. Noninsulin-treated type 2 diabetes patients do not run similar metabolic risks, but may, nevertheless, have to reduce antidiabetic medication on exercise days. All diabetes patients should undergo a medical evaluation before increasing physical activity level. During regularly repeated exercise (i.e., training) an improvement in glycemic regulation reflected in reduced HbA1c may be expected in type 2, but not type 1, patients. In both groups exercise reduces the risk of cardiovascular morbidity and increases life expectancy. Finally, exercise reduces the risk of getting type 2 diabetes.
Type 2 diabetes mellitus (T2DM), the most common form of diabetes, is characterized by insulin resistance in the hepatic and peripheral tissues. Glucose transporter 4 (GLUT4) plays a major role in the pathophysiology of T2DM. Its defective expression or translocation to the peripheral cell plasma membrane in T2DM patients hinders the entrance of glucose into the cell for energy production. In addition to suitable drugs, an appropriate diet and/or exercise can be implemented to target the increase in GLUT4 expression, GLUT4 concentrations and GLUT4 translocation to the cell surface when managing the glucose metabolism of T2DM patients. In this review, we discussed good intervention strategies that were individually administered or coupled with diet and/or exercise and may affect the expression and translocation of GLUT4 in T2DM after reducing the excess glucose load in the blood. Additionally, some potentially good synthetic and natural compounds, which can activate the insulin-independent GLUT4 signaling pathways for the efficient management of T2DM, are highlighted as possible targets or emerging alternative sources for future drug development.
Muscle atrophy is caused by an imbalance in contractile protein synthesis and degradation which can be triggered by various conditions including Type 2 Diabetes Mellitus (T2DM). Reduced muscle quality in patients with T2DM adversely affects muscle function, the capacity to perform activities of daily living, quality of life and ultimately may increase the risk of premature mortality. Systemic inflammation initiated by obesity and prolonged overnutrition not only contributes to insulin resistance typical of T2DM, but also promotes muscle atrophy via decreased muscle protein synthesis and increased ubiquitin-proteasome, lysosomal-proteasome and caspase 3- mediated protein degradation. Emerging evidence suggests that the inflammation-sensitive Nuclear Factor κ B (NF-κB) and Signal Transducer and Activator of Transcription 3 (STAT3) pathways may contribute to muscle atrophy in T2DM. In contrast, exercise appears to be an effective tool in promoting muscle hypertrophy, in part due to its effect on systemic and local (skeletal muscle) inflammation. The current review discusses the role inflammation plays in muscle atrophy in T2DM and the role of exercise training in minimising the effect of inflammatory markers on skeletal muscle. We also report original data from a cohort of obese patients with T2DM compared to age-matched controls and demonstrate that patients with T2DM have 60% higher skeletal muscle expression of the atrophy transcription factor FoxO1. This review concludes that inflammatory pathways in muscle, in particular, NF-κB, potentially contribute to T2DM-mediated muscle atrophy. Further in-vivo and longitudinal human research is required to better understand the role of inflammation in T2DM-mediated atrophy and the anti-inflammatory effect of exercise training under these conditions.
Type 2 diabetes mellitus (T2DM) is an evolving chronic health condition. Those with the disease are predisposed to other health issues, which makes disease management difficult. However, resistance training has proven effective in the management of T2DM, specifically by improving glycemic control in these individuals.
Objectives: The link between changes in leg strength per body weight and metabolic syndrome was evaluated in Japanese men with a 1-year follow up.Subjects and Methods: We used data for 136 Japanese men (45.5 ± 8.5 years) with a 1-year follow up. All subjects were given instructions by well-trained medical staff on how to change their lifestyle. Metabolic syndrome has been defined by a new criterion in Japan. The association between changes in leg strength per body weight and metabolic syndrome was evaluated.Results: With a 1-year follow up, body weight, abdominal circumference, systolic blood pressure, diastolic blood pressure and triglyceride were significantly reduced. Leg strength and leg strength per body weight and HDL cholesterol were significantly increased. The prevalence of metabolic syndrome was significantly reduced. There was significant relationship between changes in metabolic syndrome and changes in leg strength per body weight. The prevalence of metabolic syndrome was significantly reduced in subjects with an increase in leg strength per body weight (Group I) compared to subjects without such an increase (Group D). In addition, there were remarkable differences in delta abdominal circumference (delta represents positive changes in parameters) between Group I and Group D.Conclusion: An increase in leg strength per body weight may be associated with improving metabolic syndrome and abdominal circumference in Japanese men.
The aim of this study was to assess the relationship between external measures of resistance training (RT) workload and intensity, volume load (VL) and training intensity (TI), and related internal measures, session load and session rating of perceived exertion (sRPE), across a chronic RT intervention and between different models of RT in older adults. Forty-one healthy, untrained older adults (female, 21; male, 20; age, 70.9 ± 5.1 years; height, 166.3 ± 8.2 cm; weight, 72.9 ± 13.4 kg) were randomly stratified into 3 RT groups: nonperiodized (NP), block periodized (BP), or daily undulating periodized (DUP). They completed a 22-week RT intervention at a frequency of 3 d·wk-1. All training was executed on RT machines, and training volume was equalized between training groups based on total repetitions. Session RPE was measured 10-15 minutes after each training session. There were no meaningful relationships between VL and session load or TI and sRPE. Also, no significant differences were detected between training groups for mean sRPE across the training intervention. Based on these results, session load and sRPE do not appear to be valid markers of RT workload and intensity when compared with established external measures in healthy untrained older adults. However, sRPE and session load may hold promise as monitoring tools in RT that do not involve training to muscular failure. Furthermore, sRPE does not significantly differ between NP, BP, and DUP RT models, highlighting that this measure is not sensitive to such periodization as evident in the present study.
Type 2 diabetes (T2D) alters capillary hemodynamics, causes capillary rarefaction in skeletal muscle and alters endothelial and vascular smooth muscle cell phenotype. These changes contribute to altered blood flow responses to physiological stimuli such as; exercise and insulin secretion. T2D-induced microvascular dysfunction impairs glucose and insulin delivery to skeletal muscle (and other tissues such as skin and nervous), thereby reducing glucose uptake and perpetuating hyperglycemia and hypersinsulinemia. In patients with T2D, exercise training (EX) improves microvascular vasodilator and insulin signaling, and attenuates capillary rarefaction in skeletal muscle. EX-induced changes augment glucose/ insulin delivery and glucose uptake. If these adaptions occur in a sufficient amount of tissue, and skeletal muscle in particular, chronic exposure to hyperglycemia and hyperinsulinemia, and as the risk of microvascular complications in all vascular beds will decrease. We postulate that EX-programs that engage as much skeletal muscle mass, and recruit as many muscle fibers within each muscle, as possible will generate the greatest improvements in microvascular function, providing the duration of the stimulus is sufficient. Primary improvements in microvascular function occur in tissues (skeletal muscle primarily) engaged during exercise and secondary improvements in microvascular function throughout the body may result from improved blood glucose control. We propose that the added benefit of combined resistance and aerobic EX programs and of vigorous intensity EX programs is not simply "more is better". Rather, the additional benefit is the result of EX-induced adaptations in and around more muscle fibers, resulting in more muscle mass, and the associated microvasculature, being changed.
The effects of resistance training on adiponectin have thus far yielded equivocal results. However, the effect of periodized resistance training on plasma adiponectin in offspring of diabetics (OD) and non-diabetics (ND) (first degree family history) has yet to be determined. Untrained, healthy young men with and without a first degree family history of type 2 diabetes were assigned to an exercise intervention group (E) or an active control group (C). The E group performed a 12 week periodized resistance training program while the C group did not participate in any structured exercise program. Fasting plasma samples were obtained pre- and post-training. Total plasma adiponectin changed significantly in the E group (33.7 ± 14.7%, p = 0.025) but not the C group 10.8 ± 19.2%. OD subjects had significantly greater improvements in plasma adiponectin (69.3 ± 34.8%) compared to ND subjects (-3.2 ± 29.9%, p = 0.046). Regular aerobic exercise was significantly correlated with average plasma adiponectin (r = 0.32) while first degree family history of type 2 diabetes (r = -0.58) and decreases in body fat percentage (r = -0.77) were inversely correlated with average plasma adiponectin. Periodized high intensity resistance training appears to increase plasma adiponectin, particularly in individuals with a first degree family history of type 2 diabetes or those that experience a significant loss of fat mass. The direct correlation between regular aerobic exercise and adiponectin further suggests that a combination of aerobic and resistance training yields greater improvements in plasma adiponectin compared to resistance training alone.
The independent and combined associations of muscle strength and obesity on the prevalence of type 2 diabetes in Japanese men remain unclear.
Hand grip strength was cross-sectionally evaluated between 2011 and 2013 to assess muscle strength in 5039 male workers aged 40 to 64 years. Weight and height were measured, and overweight/obesity was defined as a body mass index ≥25 kg/m(2). The prevalence of type 2 diabetes, defined as fasting plasma glucose ≥126 mg/dL and/or hemoglobin A1c ≥6.5% and/or self-reported physician-diagnosed diabetes, was evaluated. Odds ratios (OR) and 95% confidence intervals (95% CI) for the prevalence of type 2 diabetes were obtained using a logistic regression model.
In total, 611 participants had type 2 diabetes, and 1763 participants were overweight/obese. After adjustment for covariates, we found an inverse association between muscle strength and the prevalence of type 2 diabetes (P for trend <0.01). In addition, when the analyses were stratified by obesity status, the multivariable-adjusted OR per 2-standard-deviation increase in muscle strength was 0.64 (95% CI, 0.49-0.83) in the overweight/obese group, compared to a weaker relationship in the normal-weight group (OR 0.79 per 2-standard-deviation increase; 95% CI, 0.60-1.06).
Dynapenia, an age-related decrease in muscle strength, is associated with increased prevalence of type 2 diabetes, and this relationship is stronger in overweight/obese middle-aged Japanese men than in normal-weight men.
What is the topic of this review? This review highlights the importance of increased vascular insulin sensitivity for maintaining glycaemic control and cardiovascular health. What advances does it highlight? We discuss the role of habitual physical activity in modulating vascular actions of insulin. Type 2 diabetes and cardiovascular disease commonly coexist. Current evidence suggests that impaired insulin signalling in the vasculature may be a common link between metabolic and cardiovascular diseases, including glycaemic dysregulation and atherosclerosis. Herein, we highlight the importance of the actions of insulin on the vasculature for glycaemic control and arterial health. In addition, we summarize and discuss findings from our group and others demonstrating that increased physical activity may be an effective approach to enhancing vascular insulin sensitivity. Furthermore, in light of the existing literature, we formulate the hypothesis that increased shear stress may be a prime mechanism through which habitual physical activity improves insulin signalling in the vasculature. Ultimately, we propose that targeting vascular insulin resistance may represent a viable strategy for improving glycaemic control and reducing cardiovascular risk in patients with type 2 diabetes.
© 2015 The Authors. Experimental Physiology © 2015 The Physiological Society.
The majority of US adults are overweight or obese, which is a primary risk factor for type 2 diabetes and other chronic diseases. Recent advances in behavioral treatment of obesity have produced significant short- and long-term weight losses that reduce the risk of type 2 diabetes and cardiovascular disease. This article reviews key components of effective behavioral treatment interventions, including diet, exercise, and behavioral and psychosocial strategies. The authors review newer treatment modalities that may enhance dissemination (Internet, smartphone) and discuss applications to clinical practice. Practitioners face multiple barriers to effectively delivering lifestyle interventions in today’s health care setting but, nonetheless, remain powerful motivators in helping patients initiate and maintain weight loss efforts that reduce the risk of type 2 diabetes and other chronic diseases.
It has previously been suggested that exercise training leads to increased whole body insulin sensitivity. However, the specific tissues and metabolic pathways involved have not been examined in vivo. By combining the euglycemic clamp with administration of glucose tracers, [3H]2-deoxyglucose (2DG), [14C]glucose, and [3H]glucose, in vivo insulin action at the whole body level and within individual tissues has been assessed in exercise-trained (ET, running 1 h/d for 7 wk) and sedentary control rats at four insulin doses. Whole body insulin sensitivity was significantly increased in ET. In addition, the skeletal muscles, soleus, red and white gastrocnemius, extensor digitorum longus (EDL), and diaphragm all showed increased sensitivity of insulin-stimulated 2DG uptake with training. With the exception of EDL, no significant difference in insulin-mediated glycogen synthesis between control and ET could be found. Therefore, the increased insulin-induced 2DG uptake observed in muscle following training is apparently directed towards glucose oxidation. In ET animals, adipose tissue exhibited a significant increase in insulin-mediated 2DG uptake and [14C]glucose incorporation into free fatty acids but there was no difference from control in any parameters measured in lung or liver. EDL and white gastrocnemius, which are not primarily involved during exercise of this type, also demonstrated increased insulin sensitivity following training. In conclusion, exercise training results in a marked increase in whole body insulin sensitivity related mainly to increased glucose oxidation in skeletal muscle. This effect may be mediated by systemic as well as local factors and is likely to be of therapeutic value in pathological conditions exhibiting insulin resistance.
The effects of 12 wk of physical training in addition to hypocaloric diet (DPT group, N = 10) on body composition, carbohydrate (CHO) tolerance, and insulin secretion and action were compared with the effects of diet therapy alone (D group, N = 8) in CHO-intolerant and non-insulin-dependent diabetic subjects.
Fat mass, fat-free mass (FFM), mean fasting plasma glucose, serum C-peptide, and insulin concentrations decreased similarly in both groups. The mean plasma glucose response to a mixed meal decreased approximately 20% in both treatment groups, and, after i.v. glucose, decreased 12% in the D group (P < 0.05), but did not change in the DPT group (NS between groups). The acute serum insulin response (0–6 min) after IG increased significantly in the DPT group only (NS between groups).
The mean basal endogenous glucose production (BEGP) decreased 17% (P < 0.025) in the DPT group and by 31% (P < 0.01) in the D group (NS between groups). Hepatic sensitivity to insulin, estimated by BEGP suppression during the euglycemic clamp, increased significantly by 25% in both groups. Total glucose disposal during the euglycemic clamp increased from 3.51 ± 0.04 milligrams of glucose per kilogram of fat-free mass per minute (mg/kg-FFM/min) to 4.45 ± 0.54 mg/kg-FFM/min (P < 0.05) in the DPT group, but no change occurred in the D group (NS between groups). Separation of total glucose disposal rates into CHO oxidative and nonoxidative rates using indirect calorimetry during the euglycemic clamp showed that the mean CHO oxidation rate increased in the D group (P < 0.05), but not in the DPT group (NS between groups). There was, however, a significant difference in the mean CHO nonoxidative rate between the two groups (P < 0.05), increasing in the DPT group but decreasing in the D group.
In both groups, the improvements in fasting plasma glucose and meal tolerance appeared to be attributable mostly to decreased BEGP, with increased hepatic sensitivity to insulin. However, glucose disposal was accomplished by different mechanisms in the two groups.
Six obese patients with recent-onset, non-insulin-dependent diabetes underwent assessment of glucose tolerance, insulin secretory capacity, and insulin-induced glucose disposal before and after 6-10 wk of intensive aerobic training while maintaining body weight. Fasting plasma glucose declined in every subject (average = -33 mg/dl), and oral glucose tolerance (3 h integrated plasma glucose) improved in five of the six (average = -74 mg X 3 h/dl) after training. Individual improvement in control of plasma glucose was directly proportional to degree of hyperglycemia before training and correlated well with an observed improvement in the early (30-min) plasma insulin response to oral glucose (all six subjects). The response of insulin action to training was highly variable; although the observed increase in average insulin-induced glucose disposal rate (M) during the euglycemic clamp did not reach statistical significance in our small cohort, the relative change in M was directly related to reduction in fasting insulin levels after training. Our results show that regular endurance exercise is effective in improving glucose homeostasis and may serve as an adjunct to other modes of treatment in recent-onset, non-insulin-dependent diabetic individuals.
This study has been designed to investigate, in five non-insulin-dependent diabetic patients, the influence of physical training (1 h a day, 7 days a wk for 6 wk, at 50-60% maximum oxygen uptake) on blood glucose control, glucose tolerance, insulin secretion, and insulin action. Physical training resulted in a significant improvement in blood glucose control, glucose tolerance, and insulin action. These results suggest that short-term intense physical training ameliorates the main metabolic derangements of non-insulin-dependent diabetes mellitus.
To evaluate the effects of an intense physical training program on abdominal fat distribution, glycemic control, and insulin sensitivity in patients with NIDDM and to determine whether branched-chain amino acid (BCAA) supplements influence these effects.
Twenty-four patients (ages 45 +/- 2 [mean +/- SE] years, BMI 30.2 +/- 0.9 kg/m2, HbA1c 7.9 +/- 0.3%) were randomly assigned to four groups: training plus BCAA supplement (n = 6), training plus placebo (n = 6), sedentary plus BCAA supplement (n = 6), and sedentary plus placebo (n = 6). Physical training consisted of a supervised 45-min cycling exercise at 75% of their oxygen uptake peak (VO2 peak) two times per week and an intermittent exercise one time per week for 2 months.
Patients who exercised increased their VO2 peak by 41% and their insulin sensitivity by 46%. Physical training significantly decreased abdominal fat evaluated by magnetic resonance imaging (umbilicus), with a greater loss of visceral adipose tissue (VAT) (48%) in comparison with the loss of subcutaneous adipose tissue (18%), but did not significantly affect body weight. The change in visceral abdominal fat was associated with the improvement in insulin sensitivity (r = 0.84, P = 0.001). BCAA supplementation had no effect on abdominal fat and glucose metabolism.
Physical training resulted in an improvement in insulin sensitivity with concomitant loss of VAT and should be included in the treatment program for patients with NIDDM.
Aerobic endurance exercise has traditionally been advocated in the treatment of type 2 diabetes, while the potential role of resistance training has often been overlooked. The aim of the present study was to determine the effect of circuit-type resistance training on blood pressure, lipids and long-term glycaemic control (HbAlc) in type 2 diabetic subjects. Thirty-eight type 2 diabetic subjects were enrolled in the study; 18 participated in a 5-month individualized progressive resistance training programme (moderate intensity, high volume) twice a week, while the remaining 20 served as controls. The exercise group showed improvements in total cholesterol (6.0 +/- .3 vs 5.3 +/- .3 mM; P < 0.01), low density lipoprotein (LDL)-cholesterol (3.90 +/- .22 vs 3.35 +/- .21 mM; P < 0.01) and triglycerides (1.91 +/- .25 vs 1.53 +/- .22 mM; P < 0.01). Also, the difference in the change in HbAlc between the groups (0.5%) achieved statistical significance (P < 0.01). Circuit-type resistance training seems to be feasible in moderately obese, sedentary type 2 diabetic subjects and the inclusion of circuit-type resistance training in exercise training programmes for type 2 diabetic subjects seems appropriate.
There are no studies comparing myocardial metabolism between endurance- and resistance-trained athletes. We used 2-deoxy-2-[18F]fluoro-D-glucose and positron emission tomography combined with the euglycemic hyperinsulinemic clamp technique to compare the ability of insulin to stimulate myocardial, skeletal muscle, and whole body glucose uptake between weight lifters (n = 8), endurance athletes (n = 8), and sedentary men (n = 9). Maximal aerobic power (ml. kg- 1. min- 1) was higher in the endurance athletes (71 +/- 2, P < 0.001) than the weight lifters (42 +/- 2) and the sedentary men (42 +/- 2). Skeletal muscle glucose uptake (micromol. kg muscle- 1. min- 1) was enhanced in the endurance athletes (125 +/- 16, P < 0.01) but was similar in weight lifters (59 +/- 12) and sedentary (63 +/- 7) men. The rate of glucose uptake per unit mass of myocardium (micromol. kg- 1. min- 1) was similarly decreased in endurance athletes (544 +/- 50) and weight lifters (651 +/- 45) compared with sedentary men (1,041 +/- 78, P < 0.001 vs. endurance athletes and weight lifters). Both groups of athletes had increased left ventricular mass. Consequently, total left ventricular glucose uptake was comparable in all groups. These data demonstrate that aerobic but not resistance training is associated with enhanced insulin sensitivity in skeletal muscle. Despite this, cardiac changes are remarkably similar in weight lifters and endurance athletes and are characterized by an increase in left ventricular mass and diminished insulin-stimulated glucose uptake per heart mass.
To determine whether the serine/threonine kinase Akt (also known as protein kinase B) is activated in vivo by insulin administration in humans, and whether impaired activation of Akt could play a role in insulin resistance, we measured the activity and phosphorylation of Akt isoforms in skeletal muscle from 3 groups of subjects: lean, obese nondiabetic, and obese type 2 diabetic. Vastus lateralis biopsies were taken in the basal (overnight fast) and insulin-stimulated (euglycemic clamp) states. Insulin-stimulated glucose disposal was reduced 31% in obese subjects and 63% in diabetic subjects, compared with lean subjects. Glycogen synthase (GS) activity in the basal state was reduced 28% in obese subjects and 49% in diabetic subjects, compared with lean subjects. Insulin-stimulated GS activity was reduced 30% in diabetic subjects. Insulin treatment activated the insulin receptor substrate-1-associated (IRS-1-associated) phosphoinositide 3-kinase (PI 3-kinase) 6.1-fold in lean, 3.7-fold in obese, and 2.4-fold in diabetic subjects. Insulin also stimulated IRS-2-associated PI 3-kinase activity 2.2-fold in lean subjects, but only 1.4-fold in diabetic subjects. Basal activity of Akt1/Akt2 (Akt1/2) and Akt3 was similar in all groups. Insulin increased Akt1/2 activity 1.7- to 2. 0-fold, and tended to activate Akt3, in all groups. Insulin-stimulated phosphorylation of Akt1/2 was normal in obese and diabetic subjects. In lean subjects only, insulin-stimulated Akt1/2 activity correlated with glucose disposal rate. Thus, insulin activation of Akt isoforms is normal in muscle of obese nondiabetic and obese diabetic subjects, despite decreases of approximately 50% and 39% in IRS-1- and IRS-2-associated PI 3-kinase activity, respectively, in obese diabetic subjects. It is therefore unlikely that Akt plays a major role in the resistance to insulin action on glucose disposal or GS activation that is observed in muscle of obese type 2 diabetic subjects.
GLUT-4 expression in individual fibers of human skeletal muscles in younger and older adults was studied. Furthermore, the dependency of insulin-stimulated glucose uptake on fiber type distribution was investigated. Fiber type distribution was determined in cryosections of muscle biopsies from 8 younger (29 yr) and 8 older (64 yr) healthy subjects, and estimates of GLUT-4 expression in individual fibers were obtained by combining immunohistochemistry and stereology. GLUT-4 was more abundantly expressed in slow compared with fast muscle fibers in both younger (P < 0.007) and older (P < 0. 001) subjects. A 25% reduction of GLUT-4 density in fast fibers (P < 0.001) and an unchanged GLUT-4 density in slow fibers were demonstrated in older compared with younger subjects. Insulin-stimulated glucose uptake rates measured by hyperinsulinemic, euglycemic clamp were not correlated with the fraction of slow fibers in the young (r = -0.45, P > 0.25) or in the elderly (r = 0. 11, P > 0.75) subjects. In conclusion, in human skeletal muscle, GLUT-4 expression is fiber type dependent and decreases with age, particularly in fast muscle fibers.
We characterized metabolic and mitogenic signaling pathways in isolated skeletal muscle from well-matched type 2 diabetic and control subjects. Time course studies of the insulin receptor, insulin receptor substrate (IRS)-1/2, and phosphatidylinositol (PI) 3-kinase revealed that signal transduction through this pathway was engaged between 4 and 40 min. Insulin-stimulated (0.6-60 nmol/l) tyrosine phosphorylation of the insulin receptor beta-subunit, mitogen-activated protein (MAP) kinase phosphorylation, and glycogen synthase activity were not altered in type 2 diabetic subjects. In contrast, insulin-stimulated tyrosine phosphorylation of IRS-1 and anti-phosphotyrosine-associated PI 3-kinase activity were reduced 40-55% in type 2 diabetic subjects at high insulin concentrations (2.4 and 60 nmol/l, respectively). Impaired glucose transport activity was noted at all insulin concentrations (0.6-60 nmol/l). Aberrant protein expression cannot account for these insulin-signaling defects because expression of insulin receptor, IRS-1, IRS-2, MAP kinase, or glycogen synthase was similar between type 2 diabetic and control subjects. In skeletal muscle from type 2 diabetic subjects, IRS-1 phosphorylation, PI 3-kinase activity, and glucose transport activity were impaired, whereas insulin receptor tyrosine phosphorylation, MAP kinase phosphorylation, and glycogen synthase activity were normal. Impaired insulin signal transduction in skeletal muscle from type 2 diabetic patients may partly account for reduced insulin-stimulated glucose transport; however, additional defects are likely to play a role.
Skeletal muscle insulin sensitivity is enhanced after acute exercise and short-term endurance training. We investigated the impact of exercise on the gene expression of key insulin-signaling proteins in humans. Seven untrained subjects (4 women and 3 men) completed 9 days of cycling at 63 +/- 2% of peak O(2) uptake for 60 min/day. Muscle biopsies were taken before, immediately after, and 3 h after the exercise bouts (on days 1 and 9). The gene expression of insulin receptor substrate-2 and the p85 alpha subunit of phosphatidylinositol 3-kinase was significantly higher 3 h after a single exercise bout, although short-term training ameliorated this effect. Gene expression of insulin receptor and insulin receptor substrate-1 was not significantly altered at any time point. These results suggest that exercise may have a transitory impact on the expression of insulin receptor substrate-2 and phosphatidylinositol 3-kinase; however, the predominant actions of exercise on insulin sensitivity appear not to reside in the transcriptional activation of the genes encoding major insulin-signaling proteins.
To determine whether defects in the insulin signal transduction cascade are present in skeletal muscle from prediabetic individuals, we excised biopsies from eight glucose-intolerant male first-degree relatives of patients with type 2 diabetes (IGT relatives) and nine matched control subjects before and during a euglycemic-hyperinsulinemic clamp. IGT relatives were insulin-resistant in oxidative and nonoxidative pathways for glucose metabolism. In vivo insulin infusion increased skeletal muscle insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation (P = 0.01) and phosphatidylinositide 3-kinase (PI 3-kinase) activity (phosphotyrosine and IRS-1 associated) in control subjects (P < 0.02) but not in IGT relatives (NS). The incremental increase in insulin action on IRS-1 tyrosine phosphorylation was lower in IGT relatives versus control subjects (P < 0.05). The incremental defects in signal transduction noted for IRS-1 and PI 3-kinase may be attributed to elevated basal phosphorylation/activity of these parameters, because absolute phosphorylation/activity under insulin-stimulated conditions was similar between IGT relatives and control subjects. Insulin increased Akt serine phosphorylation in control subjects and IGT relatives, with a tendency for reduced phosphorylation in IGT relatives (P = 0.12). In conclusion, aberrant phosphorylation/activity of IRS-1, PI 3-kinase, and Akt is observed in skeletal muscle from relatives of patients with type 2 diabetes with IGT. However, the elevated basal activity of these signaling intermediates and the lack of a strong correlation between these parameters to glucose metabolism suggests that other defects of insulin signal transduction and/or downstream components of glucose metabolism may play a greater role in the development of insulin resistance in skeletal muscle from relatives of patients with type 2 diabetes.
To examine the effect of high-intensity progressive resistance training combined with moderate weight loss on glycemic control and body composition in older patients with type 2 diabetes.
Sedentary, overweight men and women with type 2 diabetes, aged 60-80 years (n = 36), were randomized to high-intensity progressive resistance training plus moderate weight loss (RT & WL group) or moderate weight loss plus a control program (WL group). Clinical and laboratory measurements were assessed at 0, 3, and 6 months.
HbA(1c) fell significantly more in RT & WL than WL at 3 months (0.6 +/- 0.7 vs. 0.07 +/- 0.8%, P < 0.05) and 6 months (1.2 +/- 1.0 vs. 0.4 +/- 0.8%, P < 0.05). Similar reductions in body weight (RT & WL 2.5 +/- 2.9 vs. WL 3.1 +/- 2.1 kg) and fat mass (RT & WL 2.4 +/- 2.7 vs. WL 2.7 +/- 2.5 kg) were observed after 6 months. In contrast, lean body mass (LBM) increased in the RT & WL group (0.5 +/- 1.1 kg) and decreased in the WL group (0.4 +/- 1.0) after 6 months (P < 0.05). There were no between-group differences for fasting glucose, insulin, serum lipids and lipoproteins, or resting blood pressure.
High-intensity progressive resistance training, in combination with moderate weight loss, was effective in improving glycemic control in older patients with type 2 diabetes. Additional benefits of improved muscular strength and LBM identify high-intensity resistance training as a feasible and effective component in the management program for older patients with type 2 diabetes.
To determine the efficacy of high-intensity progressive resistance training (PRT) on glycemic control in older adults with type 2 diabetes.
We performed a 16-week randomized controlled trial in 62 Latino older adults (40 women and 22 men; mean +/- SE age 66 +/- 8 years) with type 2 diabetes randomly assigned to supervised PRT or a control group. Glycemic control, metabolic syndrome abnormalities, body composition, and muscle glycogen stores were determined before and after the intervention.
Sixteen weeks of PRT (three times per week) resulted in reduced plasma glycosylated hemoglobin levels (from 8.7 +/- 0.3 to 7.6 +/- 0.2%), increased muscle glycogen stores (from 60.3 +/- 3.9 to 79.1 +/- 5.0 mmol glucose/kg muscle), and reduced the dose of prescribed diabetes medication in 72% of exercisers compared with the control group, P = 0.004-0.05. Control subjects showed no change in glycosylated hemoglobin, a reduction in muscle glycogen (from 61.4 +/- 7.7 to 47.2 +/- 6.7 mmol glucose/kg muscle), and a 42% increase in diabetes medications. PRT subjects versus control subjects also increased lean mass (+1.2 +/- 0.2 vs. -0.1 +/- 0.1 kg), reduced systolic blood pressure (-9.7 +/- 1.6 vs. +7.7 +/- 1.9 mmHg), and decreased trunk fat mass (-0.7 +/- 0.1 vs. +0.8 +/- 0.1 kg; P = 0.01-0.05).
PRT as an adjunct to standard of care is feasible and effective in improving glycemic control and some of the abnormalities associated with the metabolic syndrome among high-risk older adults with type 2 diabetes.
The present study was undertaken to explore the effects of creatine and creatine plus protein supplementation on GLUT-4 and glycogen content of human skeletal muscle. This was investigated in muscles undergoing a decrease (immobilization) and subsequent increase (resistance training) in activity level, compared with muscles with unaltered activity pattern. A double-blind, placebo-controlled trial was performed by 33 young healthy subjects. The subjects' right legs were immobilized with a cast for 2 wk, followed by a 6-wk resistance training program for the right knee extensor muscles. The participants were supplemented throughout the study with either placebo (Pl group) or creatine (Cr group) or with creatine during immobilization and creatine plus protein during retraining (Cr+P group). Needle biopsies were bilaterally taken from the vastus lateralis. GLUT-4 protein expression was reduced by the immobilization in all groups (P < 0.05). During retraining, GLUT-4 content increased (P < 0.05) in both Cr (+24%) and Cr+P (+33%), which resulted in higher posttraining GLUT-4 expression compared with Pl (P < 0.05). Compared with Pl, muscle glycogen content was higher (P < 0.05) in the trained leg in both Cr and Cr+P. Supplements had no effect on GLUT-4 expression or glycogen content in contralateral control legs. Area under the glucose curve during the oral glucose tolerance test was decreased from 232 +/- 23 mmol. l(-1). min(-1) at baseline to 170 +/- 23 mmol. l(-1). min(-1) at the end of the retraining period in Cr+P (P < 0.05), but it did not change in Cr or Pl. We conclude that creatine intake stimulates GLUT-4 and glycogen content in human muscle only when combined with changes in habitual activity level. Furthermore, combined protein and creatine supplementation improved oral glucose tolerance, which is supposedly unrelated to the changes in muscle GLUT-4 expression.
Patients with non-insulin-dependent diabetes mellitus (NIDDM) exhibit insulin resistance and decreased glucose transport in skeletal muscle. Total content of muscle GLUT4 protein is not affected by NIDDM, whereas GLUT4 mRNA content is reported, variously, to be unaffected or increased. Physical training is recommended in the treatment of NIDDM, but the effect of training on muscle GLUT4 protein and mRNA content is unknown. To clarify the effect of training in NIDDM, seven men with NIDDM (58 +/- 2 years of age [mean +/- SE]) and eight healthy men (59 +/- 1 years of age) (control group) performed one-legged ergometer bicycle training for 9 weeks, 6 days/ week, 30 min/day. Biopsies were obtained from the vastus lateralis leg muscle before and after training. GLUT4 protein analyses was performed along with analyses of muscle biopsies from five young (23 +/- 1 years of age) (young group), healthy subjects who participated in a previously published identical study. in response to training, maximal oxygen uptake increased (Delta 3.3 +/- 1.8 in NIDDM subjects and 4.5 +/- 1.2 ml . min(-1) . kg(-1) in control subjects [both P < 0.05]). Before training, GLUT4 protein content was similar in NIDDM, control, and young subjects (0.35 +/- 0.02, 0.34 +/- 0.03, and 0.41 +/- 0.03 arbitrary units, respectively), and it increased (P < 0.05) in all groups during training (to 0.43 +/- 0.03, 0.40 +/- 0.03, and 0.57 +/- 0.08 arbitrary units, respectively). GLUT4 mRNA content was always lower in NIDDM compared with control subjects (P < 0.05) and increased in both groups (P < 0.05) during training (94 +/- 6 to 122 +/- 8 and 151 +/- 5 to 170 +/- 4 arbitrary units/10 mu g total RNA, respectively). me conclude that muscle GLUT4 protein and mRNA increase in both NIDDM and control subjects in response to training. GLUT4 mRNA content is lower in NIDDM subjects compared with control subjects. GLUT4 protein content does not change with age.
Classical referencePhysical inactivity and the epidemic of type 2 diabetesPhysical training as a tool to prevent and treat type 2 diabetesSummaryQuestions
The role of physical activity in the prevention of non-insulin-dependent diabetes mellitus (NIDDM) is of utmost importance. The aim of the present study was to evaluate the metabolic effects of aerobic endurance exercise and circuit-type resistance training in subjects with impaired glucose tolerance (IGT). Twenty-two individuals participated in the study. Fourteen subjects were enrolled in the aerobic endurance exercise part of the study; seven exercised regularly for six months, while seven served as controls. Maximal aerobic capacity (VO2max) was measured and insulin sensitivity and insulin secretion were assessed by a frequently sampled intravenous glucose tolerance test (FSIVGTT). Eight subjects participated in a circuit-type resistance training program for three months. Insulin sensitivity and substrate oxidation were then assessed using the euglycemic insulin clamp technique combined with indirect calorimetry. The aerobic endurance exercise program caused in increase in VO2max (21.6 +/- 1.9 to 25.4 +/- 2.4 ml/kg.min; p < 0.05) and HDL-cholesterol (1.14 +/- 0.06 to 1.23 +/- 0.08 mmol/l; p < 0.05), but no change in insulin sensitivity nor insulin secretion occurred. However, comparing the changes between the intervention and control group, the differences disappeared. Circuit-type resistance training increased insulin sensitivity (glucose disposal) by 23% (p < 0.05), primarily due to a 27% increase in non-oxidative glucose metabolism. Both circuit-type resistance training and aerobic endurance exercise seem to have beneficial effects in subjects with impaired glucose tolerance. However, by improving insulin sensitivity, circuit-type resistance training may postpone the manifestations of NIDDM in these high-risk individuals and should therefore be included in an exercise program for IGT subjects.
It is not known whether training enhances insulin sensitivity in patients with diabetes and whether this results in a greater improvement in glucose tolerance than is reported in control subjects. In an attempt to answer these questions, we assessed the effects of physical training on glucose tolerance and serum insulin in several patients with maturity-onset diabetes. This report describes the effects of 3-6 months of physical training on a bicycle ergometer in six midle-aged men in whom diabetes was associated with fasting hyperglycemia and deficient insulin secretion. The effect of the training regimen on plasma triglycerides and cholesterol is also described. In the present study, four subjects experienced a decrease in cholesterol that averaged 26 mg/dl and was not associated with a change in body weight or water. The fifth subject in whom cholesterol was determined had an increase of 20 mg/dl after training, even though his plasma triglycerides had diminished. The increment in plasma cholesterol in this individual, in part, may have been related to seasonal variation, as his initial determinations were done during the summer and his later determinations in March, when plasma levels may be in excess of 20 mg/dl higher. The results suggest that the role of physical training in the therapy of diabetes requires further consideration. Additional studies are needed to define the intensity and frequency of exercise needed to produce and maintain biochemical improvement in the diabetic. Also, it remains to be determined if certain patients will benefit more than others. Individuals with deficient insulin secretion were reported here. As training seems to enhance insulin sensitivity, it may well be that maturity-onset diabetics with hyperinsulinism and insulin resistance would show even greater improvement.
To clarify the impact of vigorous physical training on in vivo insulin action and glucose metabolism independent of the intervening effects of concomitant changes in body weight and composition and residual effects of an acute exercise session, 10 lean, 10 obese, and 6 diet-controlled type II diabetic men trained for 12 wk on a cycle ergometer 4 h/wk at approximately 70% of maximal O2 uptake (VO2max) while body composition and weight were maintained by refeeding the energy expended in each training session. Before and 4-5 days after the last training session, euglycemic hyperinsulinemic (40 mU.m2.min-1) clamps were performed at a plasma glucose of 90 mg/dl, combined with indirect calorimetry. Total insulin-stimulated glucose disposal (M) was corrected for residual hepatic glucose output. Body weight, fat, and fat-free mass (FFM) did not change with training, but cardiorespiratory fitness increased by 27% in all groups. Before and after training, M was lower for the obese (5.33 +/- 0.39 mg.kg FFM-1.min-1 pretraining; 5.33 +/- 0.46 posttraining) than for the lean men (9.07 +/- 0.49 and 8.91 +/- 0.60 mg.kg FFM-1.min-1 for pretraining and posttraining, respectively) and lower for the diabetic (3.86 +/- 0.44 and 3.49 +/- 0.21) than for the obese men (P less than 0.001). Insulin sensitivity was not significantly altered by training in any group, but basal hepatic glucose production was reduced by 22% in the diabetic men. Thus, when intervening effects of the last exercise bout or body composition changes were controlled, exercise training per se leading to increased cardiorespiratory fitness had no independent impact on insulin action and did not improve the insulin resistance in obese or diabetic men.
Physical training increases maximally insulin-stimulated glucose assimilation and 3-O-methylglucose transport in epididymal fat cells. In the present report, glucose-inhibitable cytochalasin B binding in subcellular fractions of epididymal adipocytes was measured to assess changes in number of glucose transporters induced by training. Groups of rats trained by swimming were compared to control groups of the same age, matched with respect to body weight by restricted feeding. It was found that in trained rats the number of glucose transporters in the low density microsome fractions from non-insulin-stimulated fat cells was larger than in untrained rats. In both groups of rats, insulin stimulation of adipocytes decreased the number of glucose transporters in low-density microsomes by about 60% and increased the number of glucose transporters in the plasma membrane fractions. The number of glucose transporters in the plasma membrane fractions from maximally insulin-stimulated fat cells was larger in trained rats than in control rats. [U-14C]Glucose incorporation into lipids varied in proportion to plasma membrane cytochalasin B binding per cell under all conditions tested. The results explain the enhancing effect of training on insulin responsiveness transport of hexose in fat cells.
The effects of obesity, weight reduction, and physical condition on the concentrations of glucose-6-phosphate (G-6-P) and glycogen, and the activities of glycogen synthase (GS) and lactate dehydrogenase (LD) were determined in resting vastus or gastrocnemius muscles of 40 healthy subjects. In obese women the activity of GS was 50% (P less than 0.05) lower than in lean women with similar levels of glycogen and G-6-P, whereas no difference was found in the activity of LD. Calorie restriction induced a 4.5% (P less than 0.05) decrease in body weight from 82.5 kg corresponding to a 3.2% (P less than 0.05) decrease in body mass index from 30.9 kg m-2. The total and fractional activities of glycogen synthase were increased by 50% (P less than 0.05), whereas muscle glycogen content was reduced by 40% (P less than 0.05). The G-6-P concentration and the activity of LD remained unchanged. In well-trained young men the concentrations of G-6-P and glycogen were, respectively, 250% (P less than 0.05) and 50% (P less than 0.05) higher than in non-trained. The fractional and total activities of GS were 90% (P less than 0.05) and 50% (P less than 0.05) higher, respectively, and the total activity of LD was only half (P less than 0.05) that of non-trained subjects. In conclusion, physical training enhances the activity of GS, despite a concomitantly increased glycogen content, and thus seems to exert a more efficient stimulus on glycogen synthase than weight reduction. It is indicated that physical training may provide a clinically important contribution to blood glucose reduction in hyperglycaemic conditions.
Seven middle-aged men with manifest type II diabetes mellitus underwent an endurance training programme for 10-15 weeks. The maximal aerobic capacity, as well as the endurance capacity, was improved by 10% (p less than 0.05). The intramuscular glycogen store increased by more than 80% (p less than 0.05) from 350 mumol/g dw (dry weight), and the activities of citrate synthase and 3-hydroxy-acyl-CoA dehydrogenase increased by more than 50% (p less than 0.05) and 30% (p less than 0.05). The activity of glycogen synthase was decreased by approximately 20% (p less than 0.05), whereas lactate dehydrogenase remained unchanged. Capillaries/fibre and fibre area increased by more than 50% (p less than 0.05) and 30% (p less than 0.05) leaving the area of supply constant. Training did not influence fasting blood lipids and glucose, glycosylated hemoglobin, oral glucose tolerance, and insulin response to an oral glucose load measured 72 hours post-exercise. It is concluded that patients with manifest type II diabetes, as normoglycaemic individuals, adapt to physical training. However, no persistent effect on glucohomeostasis and lipaemia is produced by short-term training in the diabetic patients.
The purpose of this investigation was to examine the relationship between an exercise program and fetal development to determine whether training could influence insulin sensitivity in the pregnant rat. Prior to impregnation one group of animals was exercise trained on a Quinton shock-stimulus rodent treadmill. The exercised group was trained to run 5 days/wk, for 2.0 h/day at 31 m/min up an 8 degree incline for 8 wk before mating. Following mating the training intensity was reduced to 27 m/min up a 5 degree incline, and the exercise period decreased to 1 h/day. On day 19 of gestation, 24 h postexercise for the trained mothers, the animals were killed in the fed state and the parametrial fat pads were removed. The parametrial depot of the trained mother was smaller than the sedentary control dam. This was due to a change in cell size and did not involve alterations in cell number. Isolated adipocytes of the parametrial fat pads were used to measure the rates of 2-deoxy-D-[3H]glucose uptake and D-[1-14C]glucose oxidation to 14CO2. The results indicated that the adipocytes from the dam trained prior to and during pregnancy were significantly (P less than 0.05) more responsive to insulin than those of animals remaining sedentary during the same period. At the maximal insulin concentration tested, the fat cells from trained mothers were able to take up and metabolize approximately twice as much glucose as the sedentary control dams. However, the increase in insulin responsiveness induced by the training program did not match the changes observed in trained nonpregnant rats of prior investigations.
Obese subjects with normal glucose tolerance (n=55), and, in another study, a group of patients with Type 2 (non-insulin-dependent) diabetes (n=33), and controls (n=13) matched for body weight and age but with normal glucose tolerance, participated in an individualized physical training program for 3 months. Under controlled dietary conditions, metabolic studies were performed before and in steady state after the last exercise session after training in the subjects showing signs of physical training in VO2 max and heart rate measurements. No changes occurred in body weight, body cell mass, body fat or adipose tissue cellularity. Oral glucose tolerance was improved in the patients with diabetes mellitus only. In both diabetic and control subjects initially elevated C-peptide concentrations decreased, while low C-peptide values increased and which was particularly pronounced in diabetic subjects with subnormal values. Peripheral insulin values did not change. Glucose disposal rate measured with the glucose clamp technique was similar in diabetic patients and control subjects. An improvement was seen at both submaximal and maximal insulin levels in both groups, correlating with improvement in glucose tolerance in the diabetic subjects.
No changes were found in adipocytes in insulin binding or the antilipolytic effect of insulin at submaximal insulin levels, but there was a normalization of a decreased glucose incorporation into triglycerides.
These results indicate that both insulin secretion and effectiveness are altered by physical training in different ways in different clinical entities. They suggest that in insulin resistant conditions with high insulin secretion (as indicated by high C-peptide concentrations) the increased peripheral insulin sensitivity is followed by a decreased insulin secretion. This is not associated with an improvement of glucose tolerance. In Type 2 diabetes with low insulin secretion, an increased insulin secretion results from physical training, perhaps due to accompanying sensitization of the autonomic nervous system. Peripheral insulin concentrations are not altered, suggesting that the extra insulin produced is captured by the liver. This mechanism, as well as the improved peripheral insulin responsiveness seen in the whole body and also seen at the cellular level, probably both contribute to an improvement in glucose tolerance.
The effects of an exercise-induced muscle glycogen reduction and an elevated muscle glycogen concentration on glucose tolerance and the insulin response to an oral glucose tolerance test (GTT) were examined. GTTs were administered to seven male subjects after 3 days on a mixed diet (C), after exhaustive exercise and 1 day on a high-fat protein diet (L-FP), after exhaustive exercise and 1 day on a mixed diet (L-M), and after exhaustive exercise and 3 days on a high-carbohydrate diet (H-CHO). The L-M treatment resulted in a significant reduction in muscle glycogen (C, 79.6 +/- 4.2 mmol/kg wet wt vs. L-M, 53.9 +/- 1.2 mmol/kg wet wt) and a 31.7% reduction in the insulin-glucose (IG) index, a measure of insulin sensitivity in vivo. Muscle glycogen was also significantly reduced by the L-FP treatment (49.1 +/- 2.4 mmol/kg wet wt), but there was no change in the IG index. Preventing a decrease in the IG index during the L-FP treatment may have been a result of elevated free fatty acids (67%) and ketones (552%) prior to the GTT. Muscle glycogen was significantly increased by the H-CHO treatment (124.8 +/- 11.1 mmol/kg wet wt); however, the IG index was not different from that of the C treatment. The results suggest that an exercise-induced reduction in muscle glycogen can improve insulin sensitivity in vivo but that this effect is diet dependent.
Bilateral biopsies from “one-leg” trained subjects were analysed for glycogen content (G), total glycogen synthetase activity (GST), synthetase I-form (GSI) and hexokinase (HK). Histochemical estimations were made of G, GST and GSI in slow twitch (ST) and fast twitch (FT) muscle fibres. Samples from the trained (T) and the untrained (U) legs were taken before and after acute exhaustive exercise and at different intervals during a 46 h recovery period when a carbohydrate enriched diet was given. Prior to exercise G levels were higher (32 %) in T-leg than in U-leg. Throughout the experiment T-leg showed higher activity for GST (35%) and HK (18%). In both U- and T-legs GSI activity increased (from 16 to 48 %) after exercise. The increase in GSI was histochemically found mainly in ST fibres in both T- and U-leg, while the staining intensity for GST was similar in ST and FT fibres. During the recovery period, G was restored and GSI gradually declined to resting values. The rate of synthesis was the same in T- and U-legs and in the two fibre types.
A modified method for enzymic synthesis of UDP-14C-glucose in high yield is described. Labeled UDPglucose is isolated by high-voltage paper electrophoresis after an alkaline phosphatase treatment of the reaction products. The synthesis gives high yields and is reproducible, and the isolation of radioactive UDPglucose from the electrophoresis is quantitative.A new assay for UDPglucose: glycogen α-4-glucosyltransferase (EC 2.4.1.11) is also described. Enzyme reaction mixtures are spotted directly on filter paper squares and washed with 66% () ethanol, and 14C-glycogen is counted in a liquid scintillation spectrometer. The method is accurate for all transferase preparations tested if corrections are applied for sample quenching. Assay time is greatly reduced and large numbers of assays can be processed with very little increase in assay time. The assay is also readily applicable to the determination of transferase-I kinase activity.It was also found that stopping the transferase-catalyzed reaction by precipitation of trichloroacetic acid insoluble protein resulted in a loss of radioactive glycogen. When crude preparations of transferase were assayed, up to 20% of the radioactivity bound to glycogen was precipitated by 6% trichloroacetic acid.
We studied the effects of body composition and maximal aerobic power on insulin sensitivity in 23 normal-weight, healthy male subjects. Eight were weight lifters, eight were long-distance runners, and seven were untrained controls. In each subject, the percentage of body weight (BW) made up of muscle and fat tissue (% muscle and % fat, respectively), the maximal aerobic power (O2max), and the tissue sensitivity to insulin were measured. The weight lifters were characterized by 35% higher % muscle as compared with the runners or controls (P < 0.01). O2max in the runners was 30–40% higher than in the weight lifters or controls (P < 0.001). During the euglycemic clamp studies, similar steady-state plasma glucose and insulin levels were achieved in each group. When calculated per total BW, the rate of glucose metabolism (M) was virtually identical in the weight lifters (10.26 ± 1.02 mg/kg BW/min) and the runners (10.03 ± 0.86 mg/kg BW/min), and 40–45% higher than in the controls (7.10 ± 0.75 mg/kg BW/min, P < 0.05). When calculated per muscle mass (Mm), only the runners had a higher than normal rate of glucose metabolism (P < 0.02). M was directly proportional to % muscle (r = 0.54, P < 0.01) and inversely related to % fat (r = −0.72, P < 0.001). The multiple linear regression analysis revealed a highly significant multivariate correlation between M and the combined effect of % muscle, % fat, and VO2max (r = 0.78, P < 0.0005). In addition, a regression equation for the predicted M was obtained as follows: M (mg/kg BW/min) = 0.697 + 0.155 % muscle − 0.312 % fat + 0.065 VO2max (ml/kg/min).
In conclusion, first, body sensitivity to insulin is directly related to muscle mass and inversely proportional to adiposity. Second, it may be possible in healthy man to predict the rate of glucose metabolism when body composition and O2max are known.
The effects of 6 weeks of thrice weekly training on glycaemic control were assessed in 20 sedentary Type 2 (non-insulin-dependent) diabetic patients and 11 control subjects matched for previous physical activity. Maximal oxygen uptake was lower in the diabetic patients than in control subjects before training (26.2 +/- 1.1 versus 32.6 +-/ 1.7 ml X kg-1 X min-1; p less than 0.001). Glycosylated haemoglobin levels decreased in the diabetic patients during the training programme (12.2 +/- 0.5 to 10.7 +/- 0.4%; p less than 0.02). Oral and intravenous glucose tolerance determined 72 h after the last exercise period showed only minimal improvement. Plasma glucose levels were, however, significantly lower at 12 h than 72 h after exercise in eight subjects tested at both time points. These data suggest than an exercise programme can produce a significant decrease in glycosylated haemoglobin levels in Type 2 diabetic males probably due, in great measure, to the cumulative effect of transient improvements in glucose tolerance which follow each individual period of exercise.
Physical training increases insulin action in skeletal muscle in healthy men. In non-insulin-dependent diabetes mellitus (NIDDM), only minor improvements in whole-body insulin action are seen. We studied the effect of training on insulin-mediated glucose clearance rates (GCRs) in the whole body and in leg muscle in seven patients with NIDDM and in eight healthy control subjects. One-legged training was performed for 10 weeks. GCR in whole body and in both legs were measured before, the day after, and 6 days after training by hyperinsulinemic (28, 88, and 480 mU x min(-1) x m(-2)), isoglycemic clamps combined with the leg balance technique. On the 5th day of detraining, one bout of exercise was performed with the nontraining leg. Muscle biopsies were obtained before and after training. Whole-body GCRs were always lower (P < 0.05) in NIDDM patients compared with control subjects and increased (P < 0.05) in response to training. In untrained muscle, GCR was lower (P < 0.05) in NIDDM patients (13 +/- 4, 91 +/- 9, and 148 +/- 12 ml/min) compared with control subjects (56 +/- 12, 126 +/- 14, and 180 +/- 14 ml/min). It Increased (P < 0.05) in both groups in response to training (43 +/- 10, 144 +/- 17, and 205 +/- 24 [NIDDM patients] and 84 +/- 10, 212 +/- 20, and 249 +/- 16 ml/min [control subjects]). Acute exercise did not increase leg GCR. In NIDDM patients, the effect of training was lost after 6 days, while the effect lasted longer in control subjects. Training increased (P < 0.05) muscle lactate production and glucose storage as well as glycogen synthase (GS) mRNA in both groups. We conclude that training increases insulin action in skeletal muscle in control subjects and NIDDM patients, and in NIDDM patients normal values may be obtained. The increase in trained muscle cannot fully account for the increase in whole-body GCR. Improvements in GCR involve enhancement of insulin-mediated increase in muscle blood flow and the ability to extract glucose. They are accompanied by enhanced nonoxidative glucose disposal and increases in GS mRNA. The improvements in insulin action are short-lived.
