Autophagy in Skeletal Muscle is Required for Exercise Training-Induced Improvement in Glucose Tolerance

2010 ◽  
Vol 42 ◽  
pp. 8
Author(s):  
Vitor A. Lira ◽  
Mitsuharu Okutsu ◽  
Yasir N. Akhtar ◽  
Mei Zhang ◽  
Zhen Yan
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Glucose Tolerance

Effect of exercise training on glucose homeostasis in normal and insulin-deficient diabetic rats

1988 ◽  
Vol 65 (2) ◽  
pp. 844-851 ◽  
Author(s):  
L. J. Goodyear ◽  
M. F. Hirshman ◽  
S. M. Knutson ◽  
E. D. Horton ◽  
E. S. Horton
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Glucose Tolerance ◽  
Glucose Uptake ◽  
Glucose Homeostasis ◽  
Plasma Glucose ◽  
Citrate Synthase ◽  
Diabetic Rats ◽  
Oral Glucose ◽  
Oral Glucose Tolerance

The effect of 8-wk of treadmill training on plasma glucose, insulin, and lipid concentrations, oral glucose tolerance, and glucose uptake in the perfused hindquarter of normal and streptozocin-treated, diabetic Sprague-Dawley rats was studied. Diabetic rats with initial plasma glucose concentrations of 200-450 mg/dl and control rats were divided into trained and sedentary subgroups. Training resulted in lower plasma free fatty acid concentrations and increased triceps muscle citrate synthase activity in both the control and diabetic rats; triglyceride concentrations were lowered by training only in the diabetic animals. Oral glucose tolerance and both basal and insulin-stimulated glucose uptake in hindquarter skeletal muscle were impaired in the diabetic rats, and plasma glucose concentrations (measured weekly) gradually increased during the experiment. Training did not improve the hyperglycemia, impaired glucose tolerance, or decreased skeletal muscle glucose uptake in the diabetic rats, nor did it alter these parameters in the normal control animals. In considering our results and those of previous studies in diabetic rats, we propose that exercise training may improve glucose homeostasis in animals with milder degrees of diabetes but fails to cause improvement in the more severely insulin-deficient, diabetic rat.

Effects of exercise training with weight loss on skeletal muscle expression of angiogenic factors in overweight and obese older men

2021 ◽  
Author(s):  
William S. Evans ◽  
Jacob B Blumenthal ◽  
James M Heilman ◽  
Alice S. Ryan ◽  
Steven J. Prior
Keyword(s):  
Skeletal Muscle ◽  
Weight Loss ◽  
Growth Factor ◽  
Exercise Training ◽  
Glucose Tolerance ◽  
Tyrosine Kinase Receptor ◽  
Oral Glucose ◽  
Vastus Lateralis Muscle ◽  
Angiogenic Growth Factor ◽  
Angiogenic Growth Factors

Low skeletal muscle capillarization is associated with impaired glucose tolerance (IGT); however, aerobic exercise training with weight loss (AEX+WL) increases skeletal muscle capillarization and improves glucose tolerance in adults with IGT. Given that expression of angiogenic growth factors mediates skeletal muscle capillarization, we sought to determine whether angiogenic growth factor levels are associated with low capillarization in those with IGT vs. normal glucose tolerance (NGT), or to the benefits of AEX+WL in both groups. Sixteen overweight or obese men 50-75 years of age completed 6 months of AEX+WL with oral glucose tolerance tests and vastus lateralis muscle biopsies for measurement of muscle vascular endothelial growth factor (VEGF), placental growth factor (PlGF), soluble fms-like tyrosine kinase receptor-1 (sFlt-1) and basic fibroblast growth factor (bFGF). At baseline, all growth factor levels were numerically lower in IGT compared with NGT, but these did not reach statistical significance (P=0.06-0.33). Following AEX+WL, aerobic capacity (VO2max) increased by 16%, while body weight and 120-minute postprandial glucose levels decreased by 10% and 15%, respectively (P ≤ 0.001 for all). There was a main effect of AEX+WL to increase VEGF (0.095±0.016 vs. 0.114±0.018 ng/µg, P<0.05), PlGF (0.004±0.001 vs. 0.005±0.001 ng/µg, P<0.05), and sFlt-1 (0.216±0.029 vs. 0.264±0.036 ng/µg, P<0.01) with overall increases driven by the IGT group. These results suggest that 6 months of AEX+WL increases skeletal muscle angiogenic growth factor levels in older, obese adults with IGT and NGT, which may contribute to our previous findings that AEX+WL increases capillarization to improve glucose tolerance in those with IGT.

Endurance exercise training decreases capillary basement membrane width in older nondiabetic and diabetic adults

1996 ◽  
Vol 80 (3) ◽  
pp. 747-753 ◽  
Author(s):  
J. R. Williamson ◽  
P. L. Hoffmann ◽  
W. M. Kohrt ◽  
R. J. Spina ◽  
A. R. Coggan ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Basement Membrane ◽  
Glucose Tolerance ◽  
Endurance Exercise ◽  
Older Men ◽  
Sedentary Control ◽  
Men And Women ◽  
Endurance Exercise Training ◽  
Older Men And Women

The objectives of these studies were to 1) evaluate the relationships among age, glucose intolerance, and skeletal muscle capillary basement membrane (CBM) width (CBMW) and 2) determine the effects of exercise training on CBMW by comparing values of young (28 +/- 4 yr) and older (63 +/- 7 yr) athletes with those of age-matched sedentary control subjects and by measuring CBMW in older men and women before and after a 9-mo endurance-exercise training program. CBMW was measured in tissue samples obtained from the gastrocnemius muscle. CBMW in sedentary 64 +/- 3-yr-old subjects was 25% thicker than in sedentary 24 +/- 3-yr-old subjects. CBMW was similar in young and older athletes and was thinner than the CBMW of age-matched sedentary control subjects. There were no differences in CBMW among older sedentary individuals with normal or impaired glucose tolerance or mild non-insulin-dependent diabetes mellitus. Nine months of endurance exercise training reduced CBMW in older men and women by 30-40%, to widths that were not different from those of the young subjects; this response was independent of glucose tolerance status. These findings suggest that habitual exercise prevents the thickening of the skeletal muscle CBM that is characteristic of advancing age. Moreover, the thickening of the CBM appears to be readily reversed as a result of exercise training, even in older individuals.

scholarly journals Ulk1, Not Ulk2, Is Required for Exercise Training-Induced Improvement of Insulin Response in Skeletal Muscle

2021 ◽  
Vol 12 ◽  
Author(s):  
Joshua C. Drake ◽  
Rebecca J. Wilson ◽  
Di Cui ◽  
Yuntian Guan ◽  
Mondira Kundu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Glucose Tolerance ◽  
Exercise Capacity ◽  
Insulin Action ◽  
Wheel Running ◽  
Insulin Response ◽  
Tolerance Test ◽  
Metabolic Adaptation ◽  
Knock Out

Unc51 like autophagy activating kinase 1 (Ulk1), the primary autophagy regulator, has been linked to metabolic adaptation in skeletal muscle to exercise training. Here we compared the roles of Ulk1 and homologous Ulk2 in skeletal muscle insulin action following exercise training to gain more mechanistic insights. Inducible, skeletal muscle-specific Ulk1 knock-out (Ulk1-iMKO) mice and global Ulk2 knock-out (Ulk2–/–) mice were subjected to voluntary wheel running for 6 weeks followed by assessment of exercise capacity, glucose tolerance, and insulin signaling in skeletal muscle after a bolus injection of insulin. Both Ulk1-iMKO and Ulk2–/– mice had improved endurance exercise capacity post-exercise. Ulk1-iMKO did not improve glucose clearance during glucose tolerance test, while Ulk2–/– had only marginal improvement. However, exercise training-induced improvement of insulin action in skeletal muscle, indicated by Akt-S473 phosphorylation, was only impaired in Ulk1-iMKO. These data suggest that Ulk1, but not Ulk2, is required for exercise training-induced improvement of insulin action in skeletal muscle, implicating crosstalk between catabolic and anabolic signaling as integral to metabolic adaptation to energetic stress.

scholarly journals Impact of short-term exercise training intensity on β-cell function in older obese adults with prediabetes

2018 ◽  
Vol 125 (6) ◽  
pp. 1979-1986 ◽  
Author(s):  
Steven K. Malin ◽  
Monique E. Francois ◽  
Natalie Z. M. Eichner ◽  
Nicole M. Gilbertson ◽  
Emily M. Heiston ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Weight Loss ◽  
Insulin Sensitivity ◽  
Exercise Training ◽  
Glucose Tolerance ◽  
Cell Function ◽  
Β Cell ◽  
Short Term ◽  
Β Cell Function ◽  
High Intensity Interval

The effect of work-matched exercise intensity on β-cell function is unknown in people with prediabetes before clinical weight loss. We determined if short-term moderate continuous (CONT) vs. high-intensity interval (INT) exercise increased β-cell function. Thirty-one subjects (age: 61.4 ± 2.5 yr; body mass index: 32.1 ± 1.0 kg/m2) with prediabetes [American Diabetes Association criteria, 75-g oral glucose tolerance test (OGTT)] were randomized to work-matched CONT (70% HRpeak) or INT (3 min 90% HRpeak and 3 min 50% HRpeak) exercise for 60 min/day over 2 wk. A 75-g 2-h OGTT was conducted after an overnight fast, and plasma glucose, insulin, C-peptide, and free fatty acids were determined for calculations of skeletal muscle [oral minimal model (OMM)], hepatic (homeostatic model of insulin resistance), and adipose (Adipose-IR) insulin sensitivity. β-Cell function was defined from glucose-stimulated insulin secretion (GSIS, deconvolution modeling) and the disposition index (DI). Glucagon-like polypeptide-1 [GLP-1(active)] and glucose-dependent insulinotropic polypeptide (GIP) were also measured during the OGTT, along with peak oxygen consumption and body composition. CONT and INT increased skeletal muscle- but not hepatic- or adipose-derived DI ( P < 0.05). Although both treatments tended to reduce fasting GLP-1(active) ( P = 0.08), early phase GLP-1(active) increased post-CONT and INT training ( P < 0.001). Interestingly, CONT exercise increased fasting GIP compared with decreases in INT ( P = 0.02). Early and total-phase skeletal muscle DI correlated with decreased total glucose area under the curve ( r = −0.52, P = 0.002 and r = −0.50, P = 0.003, respectively). Independent of intensity, short-term training increased pancreatic function adjusted to skeletal muscle in relation to improved glucose tolerance in adults with prediabetes. Exercise also uniquely affected GIP and GLP-1(active). Further work is needed to elucidate the dose-dependent mechanism(s) by which exercise impacts glycemia. NEW & NOTEWORTHY Exercise is cornerstone for reducing blood glucose, but whether high-intensity interval training is better than moderate continuous exercise is unclear in people with prediabetes before weight loss. We show that 2 wk of exercise training, independent of intensity, increased pancreatic function in relation to elevated glucagon-like polypeptide-1 secretion. Furthermore, β-cell function, but not insulin sensitivity, was also correlated with improved glucose tolerance. These data suggest that β-cell function is a strong predictor of glycemia regardless of exercise intensity.

Invited Review: Effects of acute exercise and exercise training on insulin resistance

2002 ◽  
Vol 93 (2) ◽  
pp. 788-796 ◽  
Author(s):  
Erik J. Henriksen
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Exercise Training ◽  
Glucose Tolerance ◽  
Glucose Transport ◽  
Acute Exercise ◽  
Insulin Resistant ◽  
Beneficial Effects ◽  
Glucose Transport System

Insulin resistance of skeletal muscle glucose transport is a key defect in the development of impaired glucose tolerance and Type 2 diabetes. It is well established that both an acute bout of exercise and chronic endurance exercise training can have beneficial effects on insulin action in insulin-resistant states. This review summarizes the present state of knowledge regarding these effects in the obese Zucker rat, a widely used rodent model of obesity-associated insulin resistance, and in insulin-resistant humans with impaired glucose tolerance or Type 2 diabetes. A single bout of prolonged aerobic exercise (30–60 min at ∼60–70% of maximal oxygen consumption) can significantly lower plasma glucose levels, owing to normal contraction-induced stimulation of GLUT-4 glucose transporter translocation and glucose transport activity in insulin-resistant skeletal muscle. However, little is currently known about the effects of acute exercise on muscle insulin signaling in the postexercise state in insulin-resistant individuals. A well-established adaptive response to exercise training in conditions of insulin resistance is improved glucose tolerance and enhanced skeletal muscle insulin sensitivity of glucose transport. This training-induced enhancement of insulin action is associated with upregulation of specific components of the glucose transport system in insulin-resistant muscle and includes increased protein expression of GLUT-4 and insulin receptor substrate-1. It is clear that further investigations are needed to further elucidate the specific molecular mechanisms underlying the beneficial effects of acute exercise and exercise training on the glucose transport system in insulin-resistant mammalian skeletal muscle.

Effect of exercise training and chronic glyburide treatment on glucose homeostasis in diabetic rats

1992 ◽  
Vol 72 (1) ◽  
pp. 143-148 ◽  
Author(s):  
L. J. Goodyear ◽  
M. F. Hirshman ◽  
E. D. Horton ◽  
E. S. Horton
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Glucose Tolerance ◽  
Glucose Homeostasis ◽  
Plasma Glucose ◽  
Insulin Response ◽  
Diabetic Rats ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Glucose Clearance

Exercise training and sulfonylurea treatment, either individually or in combination, were evaluated for their effects on plasma glucose concentrations, oral glucose tolerance, and glucose clearance in the perfused hindquarter of diabetic rats. Female rats that were injected with streptozocin (45 mg/kg iv) and had plasma glucose concentrations between 11 and 25 mM were considered diabetic and divided into sedentary, glyburide-treated, exercise-trained, and glyburide-treated plus exercise-trained groups. The sedentary streptozocin-treated rats were severely diabetic, as indicated by elevated glucose concentrations, impaired insulin response during oral glucose tolerance tests, and lower rates of glucose clearance in hindlimb skeletal muscle. Neither 8 wk of exercise training nor 4 wk of glyburide treatment alone improved these parameters. In contrast, the diabetic rats that were both trained and treated with glyburide showed some improvement in glucose homeostasis, as evidenced by lower plasma glucose concentrations, an enhanced insulin response to an oral glucose load, and a decrease in the severity of skeletal muscle insulin resistance compared with the diabetic controls. These data suggest that glyburide treatment or exercise training alone does not alter glucose homeostasis in severely insulin-deficient diabetic rats; however, the combination of exercise training and glyburide treatment may interact to improve glucose homeostasis in these animals.

scholarly journals Fetuin-A is linked to improved glucose tolerance after short-term exercise training in nonalcoholic fatty liver disease

2013 ◽  
Vol 115 (7) ◽  
pp. 988-994 ◽  
Author(s):  
Steven K. Malin ◽  
Anny Mulya ◽  
Ciaran E. Fealy ◽  
Jacob M. Haus ◽  
Mangesh R. Pagadala ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Liver Disease ◽  
Exercise Training ◽  
Glucose Tolerance ◽  
Fatty Liver Disease ◽  
Short Term ◽  
Fetuin A ◽  
Nonalcoholic Fatty Liver ◽  
Glut 4 Translocation

Fetuin-A is synthesized in the liver and may be associated with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes. Lifestyle-induced weight loss reduces fetuin-A, but the effect of exercise alone is unknown. We determined the effect of short-term exercise training on plasma fetuin-A in 13 (50.5 ± 3.4 yr) obese adults (body mass index, 33.3 ± 0.9 kg/m2) with clinically diagnosed NAFLD. Subjects participated in 7 days of supervised exercise training (60 min/day at ∼85% maximum heart rate) and were instructed to maintain their normal caloric and macronutrient intake. Insulin resistance was assessed by an oral glucose tolerance test. Hepatic triglyceride content (HTGC) was determined by proton MRI. We used C2C12 skeletal muscle cells to examine the direct effect of fetuin-A on 2-deoxyglucose uptake, insulin signaling [phosphorylation of Akt and AS160 (pAkt and pAS160, respectively)], and glucose transporter-4 (GLUT-4) translocation. Insulin resistance was reduced by 29% ( P < 0.05), and glucose area under the curve (AUC) was decreased by 13% ( P < 0.01) after the 7 days of exercise. Furthermore, circulating fetuin-A was decreased by 11% (4.2 ± 03 vs. 3.6 ± 0.2 nM; P < 0.02), and this change correlated with reduced insulin resistance ( r = 0.62; P < 0.04) and glucose AUC ( r = 0.58; P < 0.04). Importantly, the exercise program did not change body weight ( P = 0.12), HTGC ( P = 0.73), or aerobic capacity ( P = 0.14). In vitro experiments revealed that fetuin-A decreased skeletal muscle glucose uptake by downregulating pAkt and pAS160 and subsequent GLUT-4 translocation to the plasma membrane. Together, our findings highlight a role for fetuin-A in skeletal muscle insulin resistance and suggest that part of the exercise-induced improvement in glucose tolerance in patients with NAFLD may be due to lowering fetuin-A.

Selected Contribution: Modulation of insulin resistance and hypertension by voluntary exercise training in the TG(mREN2)27 rat

2002 ◽  
Vol 93 (2) ◽  
pp. 805-812 ◽  
Author(s):  
Tyson R. Kinnick ◽  
Erik B. Youngblood ◽  
Matthew P. O'Keefe ◽  
Vitoon Saengsirisuwan ◽  
Mary K. Teachey ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Exercise Training ◽  
Glucose Tolerance ◽  
Glucose Transport ◽  
Voluntary Exercise ◽  
Sprague Dawley ◽  
Muscle Glucose Transport

Hypertension is often accompanied by insulin resistance of skeletal muscle glucose transport. The male heterozygous TG(mREN2)27 rat, which harbors a mouse transgene for renin, displays local elevations in the renin-angiotensin system and exhibits markedly elevated systolic blood pressure (SBP). The present study was undertaken to characterize insulin-stimulated skeletal muscle glucose transport in male heterozygous TG(mREN2)27 rats and to evaluate the effect of voluntary exercise training on SBP and skeletal muscle glucose transport. Compared with normotensive Sprague-Dawley rats, TG(mREN2)27 rats displayed a 53% elevation ( P < 0.05) in SBP, a twofold increase in plasma free fatty acid levels, and an exaggerated insulin response during an oral glucose tolerance test. Moreover, insulin-mediated glucose transport (2-deoxyglucose uptake) in isolated epitrochlearis and soleus muscles of TG(mREN2)27 animals was 33 and 43% less, respectively, than in Sprague-Dawley controls. TG(mREN2)27 rats ran voluntarily for 6 wk and achieved daily running distances of 6–7 km over the final 3 wk. Training caused a 36% increase in peak aerobic capacity and a 16% reduction in resting SBP. Fasting plasma insulin (21%) and free fatty acid (34%) levels were reduced in the trained TG(mREN2)27 rats. Whole body glucose tolerance was improved in the trained TG(mREN2)27 rats and was associated with increases of 39 and 50% in insulin-mediated glucose transport in epitrochlearis and soleus muscles, respectively. Whole muscle GLUT-4 protein was increased in the soleus (23%), but not in the epitrochlearis, of trained TG(mREN2)27 rats. These data indicate that the male heterozygous TG(mREN2)27 rat is a model of both hypertension and insulin resistance. Importantly, both of these defects can be beneficially modified by voluntary exercise training.

Sign in / Sign up

Export Citation Format

Share Document