[Show abstract][Hide abstract] ABSTRACT: Skeletal muscle regeneration and hypertrophy are important adaptive responses to both physical activity and pathological stimuli. This research was performed to investigate DNA demethylation action on the late phase of muscle differentiation and early stage of hypertrophy. The epigenetic process involved in myogenesis was studied with the DNA-demethylating agent 5-azacytidine (AZA). We induced muscle differentiation in C2C12 mouse myoblasts in the presence of 5 μM AZA and growth or differentiation medium for 48, 72, and 96 h. To study a potential AZA hypertrophic effect, we stimulated 72 h differentiated myotubes with AZA for 24 h. Unstimulated cells were used as control. By western blot and immunofluorescence analysis, we examined AZA action on myogenic regulatory factors expression, hypertrophic signaling pathway and myotube morphology. During differentiation, protein levels of myogenic markers, Myf6 and Myosin Heavy Chain (MyHC), were higher in AZA stimulated cells compared to control. Myostatin and p21 analysis revealed morphological changes which reflect a tendency to hypertrophy in myotubes. In AZA stimulated neo formed myotubes, we observed that IGF-I pathway, kinases p70 S6, 4E-BP1, and ERK1/2 were activated. Furthermore, AZA treatment increased MyHC protein content in stimulated neo myotubes. Our work demonstrates that DNA demethylation could plays an important role in promoting the late phase of myogenesis, activating endocellular pathways involved in protein increment and stimulating the hypertrophic process.
[Show abstract][Hide abstract] ABSTRACT: Nutrigenomics elucidate the ability of bioactive food components to influence gene expression, protein synthesis, degradation and post-translational modifications.Resveratrol (RSV), natural polyphenol found in grapes and in other fruits, has a plethora of health benefits in a variety of human diseases: cardio- and neuroprotection, immune regulation, cancer chemoprevention, DNA repair, prevention of mitochondrial disorder, avoidance of obesity-related diseases. In skeletal muscle, RSV acts on protein catabolism and muscle function, conferring resistance against oxidative stress, injury and cell death, but its action mechanisms and protein targets in myogenesis process are not completely known. Myogenesis is a dynamic multistep process regulated by Myogenic Regulator Factors (MRFs), responsible of the commitment of myogenic cell into skeletal muscle: mononucleated undifferentiated myoblasts break free from cell cycle, elongate and fuse to form multinucleated myotubes. Skeletal muscle hypertrophy can be defined as a result of an increase in the size of pre-existing skeletal muscle fibers accompanied by increased protein synthesis, mainly regulated by Insulin Like Growth Factor 1 (IGF-1), PI3-K/AKT signaling pathways.Aim of this work was the study of RSV effects on proliferation, differentiation process and hypertrophy in C2C12 murine cells.
To study proliferative phase, cells were incubated in growth medium with/without RSV (0.1 or 25 muM) until reaching sub confluence condition (24, 48, 72 h). To examine differentiation, at 70% confluence, cells were transferred in differentiation medium both with/without RSV (0.1 or 25 muM) for 24, 48, 72, 96 hours. After 72 hours of differentiation, the genesis of hypertrophy in neo-formed myotubes was analyzed.
Data showed that RSV regulates cell cycle exit and induces C2C12 muscle differentiation. Furthermore, RSV might control MRFs and muscle-specific proteins synthesis. In late differentiation, RSV has positive effects on hypertrophy: RSV stimulates IGF-1 signaling pathway, in particular AKT and ERK 1/2 protein activation, AMPK protein level and induces hypertrophic morphological changes in neo-formed myotubes modulating cytoskeletal proteins expression.
RSV might control cell cycle promoting myogenesis and hypertrophy in vitro, opening a novel field of application of RSV in clinical conditions characterized by chronic functional and morphological muscle impairment.
Journal of Translational Medicine 12/2013; 11(1):310. · 3.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Betaine (BET) is a component of many foods, including spinach and wheat. It is an essential osmolyte and a source of methyl groups. Recent studies have hypothesized that BET might play a role in athletic performance. However, BET effects on skeletal muscle differentiation and hypertrophy are still poorly understood.
We examined BET action on neo myotubes maturation and on differentiation process, using C2C12 murine myoblastic cells. We used RT2-PCR array, Western blot and immunofluorescence analysis to study the BET effects on morphological features of C2C12 and on signaling pathways involved in muscle differentiation and hypertrophy.
We performed a dose--response study, establishing that 10 mM BET was the dose able to stimulate morphological changes and hypertrophic process in neo myotubes. RT2-PCR array methodology was used to identify the expression profile of genes encoding proteins involved in IGF-1 pathway. A dose of 10 mM BET was found to promote IGF-1 receptor (IGF-1 R) expression. Western blot and immunofluorescence analysis, performed in neo myotubes, pointed out that 10 mM BET improved IGF-1 signaling, synthesis of Myosin Heavy Chain (MyHC) and neo myotubes length.In addition, we investigated BET role on myoblasts proliferation and differentiation. During proliferation, BET did not modify C2C12 proliferative rate, but promoted myogenic induction, enhancing MyoD protein content and cellular elongation. During differentiation, BET caused an increase of muscle-specific markers and IGF-1 R protein levels.
Our findings provide the first evidence that BET could promote muscle fibers differentiation and increase myotubes size by IGF-1 pathway activation, suggesting that BET might represent a possible new drug/integrator strategy, not only in sport performance but also in clinical conditions characterized by muscle function impairment.
Journal of Translational Medicine 07/2013; 11(1):174. · 3.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Allogeneic islet transplantation (IT) provokes changes in metabolic responses and nutritional behaviors. The durability of these changes needs to be described as well as their impact on the recipients' lifestyle. The goal of this study was to investigate how islet transplantation influenced diet, exercise habits, and body composition during 10 years after IT. A retrospective study performed in 33 (14 males, 19 females) IT recipients used dietary, physical activity open- ended questionnaire and anthropometric measurements. Data were collected before transplantation, every 3 months up to the 18th and every 6 months thereafter. Data were grouped by gender and eras: pre-IT; 0-3 years; 4-6 years, and 7-10 years after IT. Reduction in body mass index (BMI) from pre-IT to 0-3 years was noted: 23.68 ± 2,18 kg/m(2) to 22.07 ± 2.94 kg/m(2) (P < .05). Increased values were observed from 0-3 years to 4-6 years in: waist circumference (WC) (76.68 ± 7.22 to 79.44 ± 7.58 cm), BMI (23,68 ± 2,18 to 22,75 ± 3,11 kg/m(2)) and weight (64.69 ± 11.98 to 67.43 ± 14 kg): (P < .03). WC increased continuously up to 7-10 years (86.33 ± 9.45 cm; P < .05). There was an average of 5.3 ± 5.6 h/wk of exercise during follow-up. From pre-IT to 0-3 years there was a 19% reduction in protein consumption (P < .05) and a 39% increase in calories from saturated fats (P < .05). A trend to reduce carbohydrates intake noted from pre-IT to 0-3 years was progressively inverted from then throughout 7-10 years (not significant). IT was associated with a significantly decreased BMI early on that it was not sustained. The subsequent weight gain and WC increase could be the result of chronic immunosuppressive therapy and/or voluntary change in eating habits. The increased consumption of carbohydrates could be related to an adaptation of a lifestyle or/and reintroduction of insulin after graft dysfunction. Active lifestyle might be result of the intensive clinical care after IT, concomitant awareness of the importance of routine physical exercise on blood glucose control, and diabetes management. Continuous follow-up of IT recipients is needed to better understand these changes and for comparison with subjects with type 1 diabetes mellitus.
[Show abstract][Hide abstract] ABSTRACT: PURPOSE: It is demonstrated that aerobic exercise plays an important role in weight loss programs for obesity by increasing 24 h metabolic rate. While aerobic exercise can result in health and fitness benefits in obese subjects, also independently of weight loss, not completely clear are the effects of bouts of hard exercise on metabolic outcomes. The aim of this study was to test the hypothesis that short-term aerobic activity with anaerobic bouts might result in a greater improvement in the management of obesity than aerobic activity alone. METHODS: We studied 16 obese subjects (eight men) during a progressive cycloergometric test up to exhaustion, before and after 4 weeks of two different training schedules (6 days/week). Insulin and glycaemia, non-esterified fatty acids (NEFA) and lactic acid were sampled. Group A (eight subjects, four men) performed an aerobic cycle workout; Group B (eight subjects, four men) performed a 25 min aerobic workout followed by 5 min of anaerobic workout. All the subjects maintained their individual eating habits. RESULTS: The post-training test showed a decrease in AUCs NEFA in Group A (p < 0.05) and an increase in Group B (p < 0.05), together with an increase in lactic acid in Group A and a decrease in Group B (p < 0.01). β-cell function (HOMA2-B) revealed a reduction only in Group A (p < 0.05). Group B achieved a greatest reduction in body fat mass than Group A (p < 0.05). CONCLUSIONS: Aerobic plus anaerobic training seem to produce a greater response in lipid metabolism and not significant modifications in glucose indexes; then, in training prescription for obesity, we might suggest at starting weight loss program aerobic with short bouts of anaerobic training to reduce fat mass and subsequently a prolonged aerobic training alone to ameliorate the metabolic profile.
European Journal of Nutrition 04/2013; · 3.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Myogenesis is a multistep process, in which myoblasts withdraw from the cell cycle, cease to divide, elongate and fuse to form multinucleated myotubes. Cell cycle transition is controlled by a family of cyclin-dependent protein kinases (CDKs) regulated by association with cyclins, negative regulatory subunits and phosphorylation. Muscle differentiation is orchestrated by myogenic regulatory factors (MRFs), such as MyoD and Myf-5. DNA methylation is crucial in transcriptional control of genes involved in myogenesis. Previous work has indicated that treatment of fibroblasts with the DNA-demethylating agent 5-azacytidine (AZA) promotes MyoD expression. We studied the effects of AZA on cell cycle regulation and MRFs synthesis during myoblast proliferation and early myogenesis phases in C2C12 cells. During the proliferation phase, cells were incubated in growth medium with 5µM AZA (GMAZA) or without AZA (GM) for 24 hours. At 70% confluence, cells were kept in growth medium in order to spontaneously achieve differentiation or transferred to differentiation medium with 5μM AZA (DMAZA) or without AZA (DM) for 12 and 24 hours. Cells used as control were unstimulated. In the proliferation phase, AZA-treated cells seemed to lose their characteristic circular shape and become elongated. The presence of AZA resulted in significant increases in the protein contents of Cyclin-D (FC:1.23 GMAZA vs GM p≤0.05), p21 (FC: 1.23 GMAZA vs GM p≤0.05), Myf-5 (FC: 1.21 GMAZA vs GM p≤0.05) and MyoD (FC: 1.20 GMAZA vs GM p≤0.05). These results propose that AZA could inhibit cell proliferation. During 12 hours of differentiation, AZA decreased the downregulation of genes involved in cell cycle arrest and in restriction point (G1 and G1/S phase) and the expression of several cyclins, E2F Transcription Factors, cyclin-dependent kinase inhibitors, specific genes responsible of cell cycle negative regulation. During 24 hours of differentiation, AZA induced an increment in the protein expression of Myf-5 (FC: 1.57 GMAZA vs GM p≤0.05), MyoD (FC: 1.14 DM vs GM p≤0.05; FC: 1.47 DMAZA vs GM p≤0.05), p21 (FC: 1.36 GMAZA vs GM p≤0.01; FC: 1.49 DM vs GM p≤0.05; FC: 1.82 DMAZA vs GM p≤0.01) and MyHC (FC: 1.40 GMAZA vs GM p≤0.01; FC: 2.39 DM vs GM p≤0.05; FC: 3.51 DMAZA vs GM p≤0.01). Our results suggest that AZA-induced DNA demethylation can modulate cell cycle progression and enhance myogenesis. The effects of AZA may open novel clinical uses in the field of muscle injury research and treatment.
International journal of biological sciences 01/2013; 9(4):391-402. · 3.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Several studies report martial arts as a good model for investigating neuroendocrine responses to competitive fighting. However, little is known on the metabolic responses elicited by elite athletes during fighting. In particular, the metabolic picture in elite athletes of martial arts is little known. AIM: In the present study, our aim was to investigate the acute effects of a session of karate practice on the glucose-insulin system. SUBJECTS AND METHODS: Ten healthy individuals (6M/4F; BMI: 22.1 ± 0.7 kg/m(2); 21.9 ± 1.1 years, mean ± SE) who practice karate in national or international competitions were enrolled. All participants completed two experimental trials in a randomised-crossover fashion. A basal blood sample was collected from each athlete to assess plasma glucose, insulin, cortisol, testosterone and catecholamines, before karate training session. In two separate days, another blood sample was collected from each participants after 3 min of real fighting (kumite) and 3 min of ritualized simulation of combat (kata). RESULTS: In both trials, plasma glucose resulted to be higher at the end the of performance compared to the basal (p < 0.001 after kumite and p < 0.02 after kata). In contrast, insulin was similar in the basal and after physical activity in the two trials. Catecholamines were higher after kata and kumite sessions with respect to the basal values (p < 0.04) and, in particular, epinephrine post-kumite values were much greater than those measured after kata. CONCLUSIONS: Our results indicate that unlike performances of karate (kumite and kata) elicit different plasma glucose increases. In particular, we found that glucose and epinephrine concentrations increased more after kumite than after kata.
[Show abstract][Hide abstract] ABSTRACT: Adipokines are known to play a fundamental role in the etiology of obesity, that is, in the impaired balance between increased feeding and decreased energy expenditure. While the adipokine-induced changes of insulin resistance in obese diabetic and nondiabetic subjects are well known, the possible role of fat source in modulating insulin sensitivity (IS) remains controversial. The aim of our study was to explore in overweight type 2 diabetic patients (T2DM) with metabolic syndrome IS in different energy storage conditions (basal and dynamic) for relating it to leptin and adiponectin. Sixteen T2DM (5/11 F/M; 59 ± 2 years; 29.5 ± 1.1 kg/m(2)) and 16 control (CNT 5/11; 54 ± 2; 29.1 ± 1.0) underwent an oral glucose tolerance test. Fasting IS was measured by QUICKI, while the dynamic one with OGIS. The insulinogenic index (IGI) described beta cell function. Also, the lipid accumulation product parameter (LAP) was assessed. LAP accounts for visceral abdominal fat and triglycerides, and it is known to be related to IS. Possible interrelationships between LAP and adipokines were explored. In T2DM and CNT, adiponectin (7.4 ± 0.5 vs. 7.8 ± 0.9 μg/mL), leptin (13.3 ± 3.0 vs. 12.4 ± 2.6 ng/mL), and QUICKI (0.33 ± 0.01 vs. 0.33 ± 0.01) were not different (P > 0.40), at variance with OGIS (317 ± 11 vs. 406 ± 13 mL/min/m(2); P = 0.006) and IGI (0.029 ± 0.005 vs. 0.185 ± 0.029 × 10(3) pmol(I)/mmol(G); P = 0.00001). LAP was 85 ± 15 cm × mg/dL in T2DM and 74 ± 10 in CNT (P > 0.1), correlated with OGIS in all subjects (R = -0.42, P = 0.02) and QUICKI (R = -0.56, P = 0.025) in T2DM. Leptin correlated with QUICKI (R = -0.45, P = 0.009), and adiponectin correlated with OGIS (R = 0.43, P = 0.015). In overweight T2DM, insulin sensitivity in basal condition appears to be multifaceted with respect to the dynamic one, because it should be more fat-related. Insulin sensitivity appears to be incompletely described by functions of fasting glucose and insulin values alone and the use of other indices, such as LAP could be suggested.
[Show abstract][Hide abstract] ABSTRACT: Seven years ago we embarked upon the adventure of the journal Sport Sciences for Health aiming to cover an area of science related to the beneficial effects of sport and physical exercise on human health . During this period we have selected for publication a total of 101 articles from nine different countries dealing with many aspects of health-related sport issues as well as more specific sport-related technical problems covering a wide array of research areas. The journal is presently at an important turning point with a change in the Editorial Board. For this reason, and as a result of both previous experience and recent evidence in the scientific (and lay) literature, it is important to ask: what are the novelties in the field of physical exercise and sport sciences?
[Show abstract][Hide abstract] ABSTRACT: Several simple measures of graft function after islet transplantation have been proposed but a comparative evaluation is lacking. Here, we compared the performance of five indices of β-cell function: β-score, transplant estimated function (TEF), homeostasis model assessment (HOMA) 2-B%, C-peptide/glucose ratio, and Secretory Units of Islets in Transplantation (SUIT).
Two cohorts of transplanted patients were analyzed. Cohort 1 consisted of 14 recipients with type 1 diabetes of islet transplantation whereas cohort 2 consisted of 21 recipients with type 1 diabetes of cultured islet cell graft. The five surrogate indices were compared against the first- and second-phase insulin response to arginine in cohort 1, and against the C-peptide response to a hyperglycemic clamp in cohort 2.
We found that the performances of the five surrogate indices were close one to each other in cohort 1. The correlation coefficients ranged 0.62 to 0.67 and 0.62 to 0.68 against the first- and second-phase insulin response to arginine, respectively. In cohort 2, we found that the β-score, TEF, C-peptide/glucose ratio, and SUIT were reasonably well correlated with the clamp response (correlation coefficients were in the range 0.71-0.81), whereas HOMA2-B% showed a modest performance (r=0.54). HOMA2-B% could not be evaluated in one patient whose fasting glucose concentration level was below the lower bound indicated by the HOMA calculator (3 mmol/L). SUIT could not be evaluated in three patients whose fasting glucose concentration was below the glucose threshold of the SUIT formula (3.43 mmol/L).
In summary, no single index outperformed the others. Nevertheless, when the benefit to cost ratio is considered, TEF stands out for its good performance at a very low cost.
[Show abstract][Hide abstract] ABSTRACT: Trimetazidine may have beneficial effects on left ventricular (LV) function in patients with systolic heart failure. The authors assessed whether long-term addition of trimetazidine to conventional treatment could improve, along with LV function, resting whole body energy metabolism in patients with chronic systolic heart failure.
Single blind randomised study.
44 patients with systolic heart failure receiving full medical treatment.
Indirect calorimetry and two-dimensional echocardiography at baseline and after 3 months.
Whole body resting energy expenditure (REE), percentage of predicted REE, LV ejection fraction (EF), NYHA class, quality of life.
Trimetazidine increased EF compared with conventional therapy alone (from 35±8% to 42±11% vs from 35±7% to 36±6%; p=0.02, analysis of variance for repeated measures). NYHA class and quality of life also improved compared with conventional therapy (p<0.0001). REE (from 1677±264 to 1580±263 kcal/day) and percentage of predicted REE (based on the Harris-Benedict equation: from 114±10% to 108±9%) decreased in the trimetazidine group, but not in the control group (REE from 1679±304 to 1690±337 kcal/day and percentage of predicted REE from 113±12% to 115±14%). The variation was different between groups (p=0.03 and 0.023, respectively).
In patients with systolic heart failure, improvement in functional class and LV function induced by middle-term trimetazidine therapy is paralleled by a reduction in whole body REE. The beneficial cardiac effects of trimetazidine may be also mediated by a peripheral metabolic effect.
[Show abstract][Hide abstract] ABSTRACT: Physical exercise induces adaptive changes leading to a muscle phenotype with enhanced performance. We first investigated whether genetic polymorphisms altering enzymes involved in DNA methylation, probably responsible of DNA methylation deficiency, are present in athletes' DNA. We determined the polymorphic variants C667T/A1298C of 5,10-methylenetetrahydrofolate reductase (MTHFR), A2756G of methionine synthase (MTR), A66G of methionine synthase reductase (MTRR), G742A of betaine:homocysteine methyltransferase (BHMT), and 68-bp ins of cystathionine β-synthase (CBS) genes in 77 athletes and 54 control subjects. The frequency of MTHFR (AC), MTR (AG), and MTRR (AG) heterozygous genotypes was found statistically different in the athletes compared with the control group (P=0.0001, P=0.018, and P=0.0001), suggesting a reduced DNA methylating capacity. We therefore assessed whether DNA hypomethylation might increase the expression of myogenic proteins expressed during early (Myf-5 and MyoD), intermediate (Myf-6), and late-phase (MHC) of myogenesis in a cellular model of hypomethylated or unhypomethylated C2C12 myoblasts. Myogenic proteins are largely induced in hypomethylated cells [fold change (FC)=Myf-5: 1.21, 1.35; MyoD: 0.9, 1.47; Myf-6: 1.39, 1.66; MHC: 1.35, 3.10 in GMA, DMA, respectively] compared with the control groups (FC=Myf-5: 1.0, 1.38; MyoD: 1.0, 1.14; Myf-6: 1.0, 1.44; MHC: 1.0, 2.20 in GM, DM, respectively). Diameters and length of hypomethylated myotubes were greater then their respective controls. Our findings suggest that DNA hypomethylation due to lesser efficiency of polymorphic MTHFR, MS, and MSR enzymes induces the activation of factors determining proliferation and differentiation of myoblasts promoting muscle growth and increase of muscle mass.
[Show abstract][Hide abstract] ABSTRACT: Lupin seed is referred to as an antidiabetic product in traditional medicine. Conglutin-γ, a lupin seed glycoprotein, was found to cause a significant plasma glucose reduction when orally administered to rats in glucose overload trials. Conglutin-γ was identified as being responsible for the claimed biological activity, and the aim of this work was to envisage its hypothetical insulin-mimetic cellular mechanism of action. Insulin is responsible for proteosynthesis control through IRS/AKT/P70S6k/PHAS1 pathways modulation, glucose homeostasis through PKC/Flotillin-2/caveolin-3/Cbl activation and muscle differentiation/hypertrophy via muscle-specific MHC gene transcription control.
To assess whether conglutin-γ modulates the same insulin-activated kinases, myoblastic C2C12 cells were incubated after 72 h of differentiation with 100 nM insulin or 0.5 mg/mL (∼10 μM) conglutin-γ. Metformin-stimulated cells were used as a positive control. The effect on the above mentioned pathways was evaluated after 5, 10, 20 and 30 min. In the control cells medium insulin, conglutin-γ and metformin were not added. We demonstrated that insulin or conglutin-γ cell stimulation resulted in the persistent activation of protein synthetic pathway kinases and increased glucose transport, glut4 translocation and muscle-specific gene transcription regulation.
Our results indicate that conglutin-γ may regulate muscle energy metabolism, protein synthesis and MHC gene transcription through the modulation of the same insulin signalling pathway, suggesting the potential therapeutic use of this natural legume protein in the treatment of diabetes and other insulin-resistant conditions, as well as the potential conglutin-γ influence on muscle cells differentiation and regulation of muscle growth.
[Show abstract][Hide abstract] ABSTRACT: ApoE is a polymorphic protein involved in the metabolism of plasma lipoproteins; the ε4 allele was shown to be associated with coronary and aortic atherosclerosis in age-dependent fashion mediated by unknown mechanisms. This study was undertaken to assess whether the apoE isoforms in humans were associated with normal glucose tolerance and with metabolic and inflammatory risk factors of CVD. ApoE genotype was assessed in 365 individuals. Of those, 309 were studied in the postabsorptive conditions and 142 of them also underwent a 3h-OGTT; 56 additional subjects were studied by means of the insulin clamp in combination with [6,6-2H2] glucose infusion. ApoE genotype frequencies were similar to those previously reported and were not influenced by age and BMI. Fasting plasma glucose, insulin, FFA, the lipid profile, surrogate markers (HOMA-IR, OGTT-derived index) as well as the clamp-derived parameters or insulin sensitivity and insulin secretion were not different by apoE genotypes. Serum adipokines concentrations (leptin, adiponectin, resistin) and markers of inflammation (serum fasting hsCRP and MCP1/CCL2) were also not different by apoE genotypes. In the subgroup of young ε4 carriers which underwent the clamp procedure, a higher fasting endogenous glucose production was detected. ApoE genotype was not associated with insulin resistance or altered insulin secretion, and no abnormalities in the typical circulating endocrine, metabolic, and inflammatory features of the insulin resistance syndrome were detected.
[Show abstract][Hide abstract] ABSTRACT: The last decade has seen much debate on ghrelin as a potential target for treating obesity. Despite a close connection between snack food intake and obesity, snacking is controversially reviewed as a good habit in a healthy nutritional regimen. The aim of the study was to evaluate whether a different nutrient composition influences postprandial ghrelin levels and glucose increments induced by 6 isoglucidic snack food. 20 healthy individuals (10 M/10 F; BMI 23.1 ± 0.5; age 33 ± 0.67 years, mean and SE) from H San Raffaele Scientific Institute and Milan University were enrolled. The subjects underwent OGTT (50 g) and 6 isoglucidic test-meal loads to assess the ghrelin circulating levels and the area under glycemic curves induced by 6 commercial snacks. 3 h after hazelnut chocolate intake, ghrelin was significantly lower than with wafer chocolate intake (p<0.002). As a response to all snacks, the glycemic curves were not different even though hazelnut chocolate showed the lowest glycemic curve. Moreover, snack fat content was found to be inversely correlated to 3-h plasma ghrelin levels (p<0.0001; R (2)=0.77) and positively associated with satiety scores (p<0.02; R (2)=0.28). Also energy load was inversely correlated to 3-h plasma ghrelin (p<0.0001; R (2)=0.73). Our results indicate that snack food administered in equivalent glucidic loads elicits postprandial ghrelin suppression and satiety ratings in different ways. Further studies are needed to elucidate the role of ghrelin as hunger-hormone in the regulation of energy balance.
Hormone and Metabolic Research 02/2011; 43(2):135-40. · 2.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study was performed to assess left ventricular (LV) energy metabolism and function in patients with type 1 diabetes with or without overt microvascular complications.
We performed cardiac Magnetic Resonance Imaging (MRI) and (31)P spectroscopy (MRS) in 24 patients with overt microvascular complications and in 15 carefully selected patients without complications in spite of a long duration of the disease (>20 years) and matched for anthropometric features. 31 healthy subjects served as a control group.
Systolic function was preserved in all study subjects. Patients with overt complications showed a higher LV wall mass/end diastolic volume ratio and altered parameters of diastolic function when compared to patients without complications and to controls. They were also characterized by lower PCr/ATP ratio (a recognized marker of energy metabolism). No effect of HbA1c was detected within groups.
In patients with type 1 diabetes 1) overt microvascular complications were associated with altered LV geometry, diastolic function and energy metabolism 2) in patients without complications and duration of disease >20 years no association with these alterations were found despite poor glycemic control. The features of this highly selected subgroup of patients demonstrated that long lasting chronic hyperglycemia per se is not sufficient to induce abnormality of cardiac energy metabolism and that additional yet to be identified (metabolic or genetic) factors must be important contributing factors.
International journal of cardiology 10/2010; 154(2):111-5. · 6.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Some obese individuals have normal insulin sensitivity. It is controversial whether this phenotype is associated with increased all-cause mortality risk.
Fifteen-year all-cause mortality data were obtained through the Regional Health Registry for 2,011 of 2,074 Caucasian middle-aged individuals of the Cremona Study, a population study on the prevalence of diabetes in Italy. Individuals were divided in four categories according to BMI (nonobese: <30 kg/m²; obese: ≥30 kg/m²) and estimated insulin resistance (insulin sensitive: homeostasis model assessment of insulin resistance <2.5; insulin resistant ≥2.5).
Obese insulin-sensitive subjects represented 11% (95% CI 8.1-14.5) of the obese population. This phenotype had similar BMI but lower waist circumference, blood pressure, fasting glucose, triglycerides, and fibrinogen and higher HDL cholesterol than obese insulin-resistant subjects. In the 15-year follow-up, 495 deaths (cardiovascular disease [CVD]: n = 221; cancer: n = 180) occurred. All-cause mortality adjusted for age and sex was higher in the obese insulin-resistant subjects (hazard ratio 1.40 [95% CI 1.08-1.81], P = 0.01) but not in the obese insulin-sensitive subjects (0.99 [0.46-2.11], P = 0.97) when compared with nonobese insulin-sensitive subjects. Also, mortality for CVD and cancer was higher in the obese insulin-resistant subjects but not in the obese insulin-sensitive subjects when compared with nonobese insulin-sensitive subjects.
In contrast to obese insulin-resistant subjects, metabolically healthy obese individuals are less common than previously thought and do not show increased all-cause, cancer, and CVD mortality risks in a 15-year follow-up study.
Diabetes care 10/2010; 34(1):210-5. · 7.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Diabetic patients suffer from impaired wound healing, characterized by only modest angiogenesis and cell proliferation. Stem cells may stimulate healing, but little is known about the kinetics of mobilization and function of bone marrow progenitor cells (BM-PCs) during diabetic wound repair. The objective of this study was to investigate the kinetics of BM-PC mobilization and their role during early diabetic wound repair in diabetic db/db mice. After wounding, circulating hematopoietic stem cells (Lin(-)c-Kit(+)Sca-1(+)) stably increased in the periphery and lymphoid tissue of db/db mice compared to unwounded controls. Peripheral endothelial progenitor cells (CD34(+)VEGFR(+)) were 2.5- and 3.5-fold increased on days 6 and 10 after wounding, respectively. Targeting the CXCR4-CXCL12 axis induced an increased release and engraftment of endogenous BM-PCs that was paralleled by an increased expression of CXCL12/SDF-1α in the wounds. Increased levels of peripheral and engrafted BM-PCs corresponded to stimulated angiogenesis and cell proliferation, while the addition of an agonist (GM-CSF) or an antagonist (ACK2) did not further modulate wound healing. Macroscopic histological correlations showed that increased levels of stem cells corresponded to higher levels of wound reepithelialization. After wounding, a natural release of endogenous BM-PCs was shown in diabetic mice, but only low levels of these cells homed in the healing tissue. Higher levels of CXCL12/SDF-1α and circulating stem cells were required to enhance their engraftment and biological effects. Despite controversial data about the functional impairment of diabetic BM-PCs, in this model our data showed a residual capacity of these cells to trigger angiogenesis and cell proliferation.
[Show abstract][Hide abstract] ABSTRACT: Il termine omeostasi — coniato intorno al 1930 dal fisiologo americano Walter Bradford Cannon e divulgato nel suo libro The Wisdom of the Body — designa l’attitudine degli esseri viventi a mantenere entro ristretti margini di variazione i valori di grandezze fisiologiche
(ad esempio, la temperatura, l’equilibrio acido-base, la glicemia). Cannon sviluppò il concetto di omeostasi partendo dall’idea
di Claude Bernard del milieu interieur, ossia di un ambiente interno all’organismo la cui costanza è essenziale per il mantenimento della vita. Attorno al 1935, Rudolph Schoenheimer affinò questa intuizione dal punto di vista teorico formulando il concetto di stato dinamico dei costituenti corporei. L’idea portante è che la concentrazione di una sostanza nell’organismo è funzione di tre processi che avvengono in esso
simultaneamente: produzione, distribuzione, utilizzazione. Il continuo rinnovamento dei livelli circolanti della sostanza
nell’organismo è chiamato turnover. Schoenheimer fu un pioniere nell’uso di isotopi radioattivi e stabili per studiare il
turnover di proteine e lipidi nell’animale ed esercitò una straordinaria influenza sulle successive generazioni di biochimici.