[show abstract][hide abstract] ABSTRACT: Hypertension is associated with substantial morbidity in Japan. The aim of this work was to evaluate whether hypertension is associated with white matter microstructural changes by using diffusional kurtosis imaging (DKI).
We explored the regional patterns of white matter alteration in 15 hypertensive middle-aged male participants and 11 normotensive controls by using DKI-based whole-brain analysis. In addition, we investigated whether the observed white matter microstructural changes were related to systolic or diastolic blood pressure by using Pearson's correlation coefficient analysis.
Mean diffusional kurtosis (MDK) values were significantly higher in hypertensive participants than in normotensive participants (P < 0.05; family-wise error correction for multiple comparisons), indicating widespread microstructural changes in white matter. Moreover, we noted a statistically significant positive correlation between systolic and diastolic blood pressure and MDK values of the whole brain.
Our study suggests that microstructural white matter changes occur in middle-aged men with hypertension, even before the onset of cerebrovascular disease. Thus, DKI might be used as a screening tool for risk of cerebrovascular disease. This highlights the need to further elucidate the relationship between hypertension and DKI of the brain.
Japanese journal of radiology 01/2014; · 0.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Exercise enhances insulin sensitivity in skeletal muscle, but the underlying mechanism remains obscure. Recent data suggest that alternatively activated M2 macrophages enhance insulin sensitivity in insulin target organs such as adipose tissue and liver. Therefore, the aim of this study was to determine the role of anti-inflammatory M2 macrophages in exercise-induced enhancement of insulin sensitivity in skeletal muscle. C57BL6J mice underwent a single bout of treadmill running (20 m/min, 90 min). Twenty-four hours later, ex vivo insulin-stimulated 2-deoxy glucose uptake was found to be increased in plantaris muscle. This change was associated with increased number of CD163-expressing macrophages (i.e., M2-polarized macrophages) in skeletal muscle. Systemic depletion of macrophages by pretreatment of mice with clodronate-containing liposome abrogated both CD163-positive macrophage accumulation in skeletal muscle as well as the enhancement of insulin sensitivity after exercise, without affecting insulin-induced phosphorylation of Akt and AS160 or exercise-induced GLUT4 expression. These results suggest that accumulation of M2-polarized macrophages is involved in exercise-induced enhancement of insulin sensitivity in mouse skeletal muscle, independently of the phosphorylation of Akt and AS160 and expression of GLUT4.
Biochemical and Biophysical Research Communications 10/2013; · 2.41 Impact Factor
[show abstract][hide abstract] ABSTRACT: Recent genome-wide association studies demonstrated that common variants of solute carrier family 30 member 8 gene (SLC30A8) increase susceptibility to type 2 diabetes. SLC30A8 encodes zinc transporter-8 (ZnT8), which delivers zinc ion from the cytoplasm into insulin granules. Although it is well known that insulin granules contain high amounts of zinc, the physiological role of secreted zinc remains elusive. In this study, we generated mice with β cell-specific Slc30a8 deficiency (ZnT8KO mice) and demonstrated an unexpected functional linkage between Slc30a8 deletion and hepatic insulin clearance. The ZnT8KO mice had low peripheral blood insulin levels, despite insulin hypersecretion from pancreatic β cells. We also demonstrated that a substantial amount of the hypersecreted insulin was degraded during its first passage through the liver. Consistent with these findings, ZnT8KO mice and human individuals carrying rs13266634, a major risk allele of SLC30A8, exhibited increased insulin clearance, as assessed by c-peptide/insulin ratio. Furthermore, we demonstrated that zinc secreted in concert with insulin suppressed hepatic insulin clearance by inhibiting clathrin-dependent insulin endocytosis. Our results indicate that SLC30A8 regulates hepatic insulin clearance and that genetic dysregulation of this system may play a role in the pathogenesis of type 2 diabetes.
The Journal of clinical investigation 09/2013; · 15.39 Impact Factor
[show abstract][hide abstract] ABSTRACT: Ectopic fat accumulation plays important roles in various metabolic disorders and cardiovascular diseases. Recent studies reported that myocardial triglyceride (TG) content measured by proton magnetic resonance spectroscopy ((1)H-MRS) is associated with aging, diabetes mellitus, and cardiac dysfunction. However, myocardial TG content in athletes has not yet been investigated. We performed (1)H-MRS and cardiac magnetic resonance imaging in 10 male endurance athletes and 15 healthy male controls. Serum markers and other clinical parameters including arterial stiffness were measured. Cardiopulmonary exercise testing was also performed. There were no significant differences in clinical characteristics including age, anthropometric parameters, blood test results, or arterial stiffness between the two groups. Peak oxygen uptakes, end-diastolic volume (EDV), end-systolic volume (ESV), left ventricular (LV) mass, peak ejection rates and peak filling rates were significantly higher in the athlete group than in the control group (all P<0.02). Myocardial TG content was significantly lower in the athlete group than in the control group (0.60±0.20 vs. 0.89±0.41%, P<0.05). Myocardial TG content was negatively correlated with EDV (r = -0.47), ESV (r = -0.64), LV mass (r = -0.44), and epicardial fat volume (r = 0.47) (all P<0.05). In conclusion, lower levels of myocardial TG content were observed in endurance athletes and were associated with morphological changes related to physiological LV alteration in athletes, suggesting that metabolic imaging for measurement of myocardial TG content by (1)H-MRS may be a useful technique for noninvasively assessing the "athlete's heart".
PLoS ONE 01/2013; 8(4):e61604. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: OBJECTIVE
We explored the regional pattern of white matter alteration in subjects with metabolic syndrome. We also investigated whether white matter alteration was correlated with BMI.RESEARCH DESIGN AND METHODS
Seven middle-aged men with metabolic syndrome and seven without metabolic syndrome underwent diffusion tensor imaging with a 3T magnetic resonance imaging imager. We analyzed the fractional anisotropy (FA) values by using a tract-based spatial statistics technique (whole-brain analysis). We subsequently focused on measuring the mean FA values of the right inferior fronto-occipital fasciculus (IFOF) of all subjects by tract-specific analysis (regional brain analysis). We used Pearson correlation coefficient to evaluate the relationship between BMI and mean FA values of the right IFOF.RESULTSIn the whole-brain analysis, subjects with metabolic syndrome had significantly lower FA values than control subjects in part of the right external capsule (part of the right IFOF), the entire corpus callosum, and part of the deep white matter of the right frontal lobe. In the regional brain analysis, the mean FA value of the right IFOF was 0.41 ± 0.03 for subjects with metabolic syndrome and 0.44 ± 0.05 for control subjects. A significant negative correlation was observed between BMI and FA values in the right IFOF (r = -0.56, P < 0.04).CONCLUSIONS
Our results show that microstructural white matter changes occur in patients with metabolic syndrome. FA values may be useful indices of white matter alterations in patients with metabolic syndrome.
[show abstract][hide abstract] ABSTRACT: We document the first reported case of attempted suicide with the GLP-1 receptor agonist, liraglutide. A 33-year-old Japanese woman with type 2 diabetes reported subcutaneously injected 72mg of liraglutide. She experienced gastrointestinal symptoms but no hypoglycemia.
Diabetes research and clinical practice 11/2012; · 2.74 Impact Factor
[show abstract][hide abstract] ABSTRACT: Retinoid X receptor (RXR) γ is a nuclear receptor-type transcription factor expressed mostly in skeletal muscle, and regulated by nutritional conditions. Previously, we established transgenic mice overexpressing RXRγ in skeletal muscle (RXRγ mice), which showed lower blood glucose than the control mice. Here we investigated their glucose metabolism.
RXRγ mice were subjected to glucose and insulin tolerance tests, and glucose transporter expression levels, hyperinsulinemic-euglycemic clamp and glucose uptake were analyzed. Microarray and bioinformatics analyses were done. The glucose tolerance test revealed higher glucose disposal in RXRγ mice than in control mice, but insulin tolerance test revealed no difference in the insulin-induced hypoglycemic response. In the hyperinsulinemic-euglycemic clamp study, the basal glucose disposal rate was higher in RXRγ mice than in control mice, indicating an insulin-independent increase in glucose uptake. There was no difference in the rate of glucose infusion needed to maintain euglycemia (glucose infusion rate) between the RXRγ and control mice, which is consistent with the result of the insulin tolerance test. Skeletal muscle from RXRγ mice showed increased Glut1 expression, with increased glucose uptake, in an insulin-independent manner. Moreover, we performed in vivo luciferase reporter analysis using Glut1 promoter (Glut1-Luc). Combination of RXRγ and PPARδ resulted in an increase in Glut1-Luc activity in skeletal muscle in vivo. Microarray data showed that RXRγ overexpression increased a diverse set of genes, including glucose metabolism genes, whose promoter contained putative PPAR-binding motifs.
Systemic glucose metabolism was increased in transgenic mice overexpressing RXRγ. The enhanced glucose tolerance in RXRγ mice may be mediated at least in part by increased Glut1 in skeletal muscle. These results show the importance of skeletal muscle gene regulation in systemic glucose metabolism. Increasing RXRγ expression may be a novel therapeutic strategy against type 2 diabetes.
PLoS ONE 01/2011; 6(5):e20467. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Aims/Introduction: Accumulation of intramyocellular lipid (IMCL) is associated with insulin resistance. However, the factors affecting the change in IMCL remain to be elucidated. The aim of the present study was to determine the factors that influence the change in IMCL level after high-fat loading.Materials and Methods: The study subjects were 37 non-obese men. Each subject consumed a high-fat diet for 3 days after a normal-fat diet for 3 days. After each diet program, IMCL levels in the tibialis anterior (TA-IMCL) and soleus (SOL-IMCL) were measured by proton magnetic resonance spectroscopy. Glucose infusion rate (GIR) was evaluated by euglycemic hyperinsulinemic clamp as an index of peripheral insulin sensitivity.Results: The high-fat diet significantly increased TA-IMCL and SOL-IMCL by ∼30 and ∼20%, respectively (P < 0.05), whereas it did not significantly alter GIR. The increase in SOL-IMCL, but not in TA-IMCL, negatively correlated with serum high molecular weight (HMW)-adiponectin (r = −0.36, P < 0.05) and HMW-/total-adiponectin ratio (r = −0.46, P < 0.05). Although high-fat diet-related changes in SOL-IMCL showed high inter-individual variations, in subjects doing exercise, changes in SOL-IMCL (r = 0.55, P < 0.05) and TA-IMCL (r = 0.61, P < 0.05) positively correlated with daily physical activity level. In contrast, in sedentary subjects, changes in SOL-IMCL (r = −0.50, P < 0.01) and TA-IMCL (r = −0.48, P < 0.05) negatively correlated with daily physical activity.Conclusions: HMW-adiponectin and daily physical activity are determinants of IMCL accumulation by a high-fat diet. Intriguingly, the effect of daily physical activity on the change in IMCL depends on the level of regular exercise. (J Diabetes Invest,doi: 10.1111/j.2040-1124.2010.00091.x, 2011)
Journal of Diabetes Investigation. 12/2010; 2(4):310 - 317.
[show abstract][hide abstract] ABSTRACT: Repetitive blood flow restriction prevents muscular atrophy and weakness induced by chronic unloading. However, it was unclear which external compressive force for blood flow restriction was optimal to prevent muscular dysfunction. The present study was intended to investigate the effects of repeated muscle blood flow restriction at low pressure on muscular weakness induced by immobilization without weight bearing. Using casts, the left ankles of 11 healthy males were immobilized for 2 weeks. Subjects were instructed to walk using crutches with no weight bearing during the period. Subjects were divided randomly into two groups: a restriction of blood flow (RBF) group (application of external compressive force of 50 mm Hg) and a control (CON) group (no intervention). We measured changes in the muscle strength of the knee extensor-flexor and ankle plantar flexor. The percent changes in knee extensor torque at 60°/s under eccentric contraction in the RBF group were significantly smaller than in the CON group (-12.5±10.7% and -30.1±10.9%, p<0.05). The percent changes in knee flexor torque when performing an eccentric contraction at 60°/s, an isometric contraction, or a concentric contraction at both 60 and 300°/s in the RBF group were significantly smaller than those in the CON group (p<0.05). In conclusion, our results show that repetitive restriction of blood flow with 50 mm Hg cuff pressure to the lower extremity reduces muscular weakness induced by chronic unloading.
Journal of science and medicine in sport / Sports Medicine Australia. 10/2010; 14(2):95-9.
[show abstract][hide abstract] ABSTRACT: Elite athletic endurance ability involves multiple genetic and environmental factors, with little known about the specific genotypes involved. As a first step to finding genetic markers of endurance performance, we recruited 66 male endurance runners and 110 control athletes. We investigated the distribution of m.5178CA polymorphisms in male endurance runners. Although the m.5178A genotype has been reportedly associated with longevity, endurance runners in this study showed a significantly higher frequency (71.2%) of the m.5178C genotype than control subjects (52.7%). The-m.5178C genotype may be favorable for performance in elite endurance runners.
Metabolism: clinical and experimental 09/2009; 59(1):62-3. · 3.10 Impact Factor
[show abstract][hide abstract] ABSTRACT: Recent studies identified accumulation of reactive oxygen species (ROS) as a common pathway causing insulin resistance. However, whether and how the reduction of ROS levels improves insulin resistance remains to be elucidated. The present study was designed to define this mechanism.
We investigated the effect of overexpression of superoxide dismutase (SOD)1 in liver of obese diabetic model (db/db) mice by adenoviral injection.
db/db mice had high ROS levels in liver. Overexpression of SOD1 in liver of db/db mice reduced hepatic ROS and blood glucose level. These changes were accompanied by improvement in insulin resistance and reduction of hepatic gene expression of phosphoenol-pyruvate carboxykinase and peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha), which is the main regulator of gluconeogenic genes. The inhibition of hepatic insulin resistance was accompanied by attenuation of phosphorylation of cAMP-responsive element-binding protein (CREB), which is a main regulator of PGC-1alpha expression, and attenuation of Jun NH(2)-terminal kinase (JNK) phosphorylation. Simultaneously, overexpression of SOD1 in db/db mice enhanced the inactivation of forkhead box class O1, another regulator of PGC-1alpha expression, without the changes of insulin-induced Akt phosphorylation in liver. In hepatocyte cell lines, ROS induced phosphorylation of JNK and CREB, and the latter, together with PGC-1alpha expression, was inhibited by a JNK inhibitor.
Our results indicate that the reduction of ROS is a potential therapeutic target of liver insulin resistance, at least partly by the reduced expression of PGC-1alpha.
[show abstract][hide abstract] ABSTRACT: To our knowledge, there is currently no insulin infusion protocol for critically ill patients especially designed for Asian diabetics although many such protocols are used in Western countries. In this study, we modified the Yale insulin infusion protocol taking into consideration the characteristics of Japanese diabetics and hospital environment. We tested the modified protocol in 40 type 2 diabetic patients after elective open-heart surgery (MY group) comparing with 35 type 2 diabetic patients under empirical blood glucose control (EC group). Analyses of 1656 blood glucose measurements during insulin infusion revealed that percentage of samples that showed achievement of target blood glucose level (80-140 mg/dl) was higher under MY (78+/-15%, n=870) than EC (57+/-23%, n=786, p<0.0001). On the other hand, the percentage of samples in which blood glucose was less than 60 mg/dl was comparable in the two groups (MY: 0.5+/-5.9 per thousand, EC: 5.1+/-18.5 per thousand). None of the patients with hypoglycemia showed significant clinical adverse effects. In conclusion, our modified Yale insulin infusion protocol is effective and safe for tight blood glucose control in Japanese diabetic patients after open-heart surgery.
Diabetes research and clinical practice 06/2008; 81(3):296-302. · 2.74 Impact Factor
[show abstract][hide abstract] ABSTRACT: The effect of short-term fat loading on intramyocellular lipid (IMCL) in different types of muscle in endurance runners and sprinters has not been fully elucidated yet. The purpose of this study was to investigate the effect of dietary lipid on IMCL in soleus muscle (SOL) and tibialis anterior muscle (TA) during training period in endurance runners and sprinters. Seven male endurance runners and 7 male sprinters were selected to participate in the study. We measured TA- and SOL-IMCL levels after 3-day course of isocaloric normal- (25%), high- (60%), and low-fat (10%) diet during training period by (1)H-magnetic resonance spectroscopy in each subject. In sprinters, TA- and SOL-IMCL levels were comparable after each diet protocol. However, in endurance runners, TA-IMCL levels after normal-fat and high-fat diets were 1.7 times and 3.0 times higher than that after low-fat diet, respectively. The SOL-IMCL values after normal-fat diet and high-fat diet were 1.5 times and 1.6 times higher than that after low-fat diet, respectively. In addition, the TA-IMCL level after high-fat diet, but not SOL-IMCL, was significantly higher compared with that after normal-fat diet. Our data suggested that short-term dietary fat challenge during training period significantly altered IMCL level in endurance runners, but not in sprinters. In addition, response to fat loading on IMCL was influenced by variation of muscle type in endurance runners. These phenotypic and regional differences might be explained by differences in type of exercise training and muscle fiber composition.
[show abstract][hide abstract] ABSTRACT: The aim of the present study was to compare the effects of periodic restriction of blood flow to lower extremities with those of isometric exercise on disuse muscular atrophy and weakness induced by immobilization and unloading.
The left ankle of each of 15 healthy males was immobilized for 2 wk using cast, and subjects were instructed to walk using crutches with non-weight bearing during this period. Subjects were divided into three groups: a restriction of blood flow (RBF) group (application of external compressive force of 200 mm Hg for 5 min followed by 3 min of rest, repeated five times in a single session, two sessions per day for 14 d); an isometric training (IMT) group (20 "exercises" of 5-s isometric contraction of the knee extensor, flexor, and ankle plantar flexor muscles followed by rest, twice a day, daily for 2 wk); and a control (CON) group (no intervention). We measured changes in muscle strength, thigh/leg circumferences, and serum growth hormone levels.
Immobilization/unloading resulted in significant decreases in muscle strength of knee extensor and flexor muscles (P < 0.01 and < 0.05, respectively) and thigh and leg circumferences (P < 0.05, each) in the CON group, and significant decreases in muscle strength of the knee flexor muscles, ankle plantar flexor muscles, and leg circumference (P < 0.05) in the IMT group. RBF protected against these changes in muscle strength and thigh/leg circumference (P < 0.01 and < 0.05, respectively). No changes in serum growth hormone levels were noted.
Our results indicate that repetitive restriction of blood flow to the lower extremity prevents disuse muscular weakness.
Medicine & Science in Sports & Exercise 04/2008; 40(3):529-34. · 4.48 Impact Factor
[show abstract][hide abstract] ABSTRACT: Postprandial hyperglycemia observed in type 2 diabetes mellitus is a risk factor for atherosclerosis. The aim of this study was to investigate the effect of strict glycemic control by nateglinide on common carotid far wall intima-media thickness in type 2 diabetic patients who were already under good glycemic control.
We performed an open labeled randomized prospective trial on 78 drug-naive type 2 diabetic patients whose HbA1c was less than 6.5%. Thirty-eight patients were randomly assigned to receive nateglinide (270 mg/dL) and 40 to control group (no treatment). After 12 months, a significant reduction in HbA1c was observed in the nateglinide group, whereas a significant increase of HbA1c was observed in the untreated group. The carotid intima-media thickness at the end of 1-year follow-up was significantly reduced in the nateglinide group compared with the untreated group (-0.017+/-0.054 mm/year versus 0.024+/-0.066 mm/year, P=0.0064). Whereas nateglinide treatment also reduced triglyceride, highly-sensitive C-reactive protein, and E-selectin, multiple regression analysis identified HbA1c as the only significant independent determinant of the change in carotid intima-media thickness.
In type 2 diabetic patients with good glycemic control, further strict glycemic control by nateglinide results in regression of carotid intima-media thickness.
[show abstract][hide abstract] ABSTRACT: Previous studies have demonstrated that a low-intensity resistance exercise, combined with vascular occlusion, results in a marked increase in muscular size and strength. We investigated the optimal pressure for reduction of muscle blood flow with resistance exercise to increase the muscular strength and endurance. Twenty-one subjects were randomly divided into four groups by the different application of vascular occlusion pressure at the proximal of thigh: without any pressure (0-pressure group), with a pressure of 50mmHg (50-pressure group), with a pressure of 150mmHg (150-pressure group), and with a pressure of 250mmHg (250-pressure group). The isokinetic muscle strength at angular velocities of 60 and 180 degrees /s, total muscle work, and the cross-sectional knee extensor muscle area were assessed before and after exercise. Exercise was performed three times a week over an 8-week period at an intensity of approximately 20% of one-repetition maximum for straight leg raising and hip joint adduction and maximum force for abduction training. A significant increase in strength at 180 degrees /s was noted after exercise in all subjects who exercised under vascular occlusion. Total muscle work increased significantly in the 50- and 150-pressure groups (P<0.05, P<0.01, respectively). There was no significant increase in cross-sectional knee extensor muscle area in any groups. In conclusion, resistance exercise with relatively low vascular occlusion pressure is potentially useful to increase muscle strength and endurance without discomfort.
Journal of Science and Medicine in Sport 12/2007; 12(1):107-12. · 2.90 Impact Factor
[show abstract][hide abstract] ABSTRACT: We report a 60-year-old Japanese patient with glycogen storage disease type 1a (GSD1a) who was thoroughly evaluated for risk factors of atherosclerosis. As often observed in patients with GSD1a, this patient has multiple risk factors for atherosclerosis including hyperlipidemia, hypertension, glucose intolerance with insulin resistance, and chronic kidney disease. However, she lacked clinically evident atherosclerosis as generally observed in GSD1a patients. Unexpectedly, this patient had marked hyperadiponectinemia (27.6 microg/mL; reference range, 4.1-18.9 microg/mL) with increase in the ratio of high-molecular weight to total adiponectin. Although the reason for the hyperadiponectinemia was not clear, at least it seemed to protect against enhanced atherosclerogenesis otherwise promoted by a battery of risk factors. Although further studies are needed, hyperadiponectinemia in addition to hypoinsulinemia might explain at least in part the lack of evident atherosclerosis in patients with GSD1a.
[show abstract][hide abstract] ABSTRACT: Recent studies suggest that insulin resistance is associated with increased intrahepatic lipid (IHL) and intramyocellular lipid (IMCL) contents. While metformin improves insulin resistance mainly in liver, its effects on IHL and IMCL have not been clarified yet. The aim of this study was to investigate the effects of low-dose metformin (750 mg/day) on peripheral insulin sensitivity, IHL and IMCL.
Before and 3 months after low-dose metformin therapy, eight overweight/obese Japanese subjects [body mass index (BMI) >25 kg/m2] were studied with blood sampling, measurement of IHL and IMCL by 1H magnetic resonance spectroscopy and glucose infusion rate (GIR) during euglycaemic-hyperinsulinaemic clamp as an index of peripheral insulin sensitivity.
A 3-month low-dose metformin therapy did not alter body weight, total body fat, fat distribution or physical activity level but increased GIR by 31% (from 6.24 +/- 0.86 to 7.82 +/- 0.82 mg/kg/min, p < 0.01). Although metformin treatment did not alter IMCL (from 4.1 +/- 1.0 to 4.2 +/- 0.9, not significant), it decreased IHL by 21% (from 15.9 +/- 2.8 to 11.8 +/- 2.2%, p < 0.05).
A 3-month low-dose metformin treatment improved peripheral insulin sensitivity and reduced IHL, without significantly changing BMI, adiposity or IMCL.
Diabetes Obesity and Metabolism 11/2007; 10(9):733-8. · 5.18 Impact Factor
[show abstract][hide abstract] ABSTRACT: Although moderate weight reduction is recommended as primary therapy of metabolic syndrome, little information is known regarding metabolic changes associated with moderate weight reduction in nondiabetic obese subjects.
The aim of this study was to determine the effects of a moderate weight reduction program on intracellular lipid and glucose metabolism in muscle and liver.
Data for 13 nondiabetic obese subjects were evaluated.
Subjects were put on a 3-month mildly hypocaloric diet therapy (approximately 35 kcal/kg of ideal body weight).
Intrahepatic lipid (IHL) and intramyocellular lipid were measured by using (1)H magnetic resonance spectroscopy. Peripheral insulin sensitivity and splanchnic glucose uptake were evaluated by euglycemic-hyperinsulinemic clamp with oral glucose load.
Diet therapy for 3 months resulted in 6% reduction in body weight (from 99.9 +/- 7.3 to 93.8 +/- 6.6 kg, P < 0.0001). This change was accompanied by reduction of plasma glucose and insulin excursions during 75-g oral glucose tolerance tests, decrease in diastolic blood pressure, glycated hemoglobin, serum low-density lipoprotein cholesterol, and triglyceride. These changes were also accompanied by a decrease in IHL (from 12.9 to 8.2%, P < 0.01) and increase in splanchnic glucose uptake (from 13.5 to 35.0%, P < 0.03). On the other hand, the diet program did not affect intramyocellular lipid or glucose infusion rate during euglycemic hyperinsulinemic clamp.
Our results suggest that moderate weight reduction in obese subjects decreased IHL and augmented splanchnic glucose uptake. This mechanism is at least in part involved in improvement of glucose metabolism by moderate weight reduction in obese subjects.