scholarly journals The effect of exercise training combined with PPARγ agonist on skeletal muscle glucose uptake and insulin sensitivity in induced diabetic obese Zucker rats

2016 ◽  
Vol 20 (2) ◽  
pp. 42-50 ◽  
Author(s):  
Jae-Cheol Kim
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Exercise Training ◽  
Glucose Uptake ◽  
Zucker Rats ◽  
Pparγ Agonist ◽  
Skeletal Muscle Glucose Uptake ◽  
Obese Zucker Rats

scholarly journals Exercise training increases ERK2 activity in skeletal muscle of obese Zucker rats

2001 ◽  
Vol 90 (2) ◽  
pp. 454-460 ◽  
Author(s):  
Abdullah A. Osman ◽  
Joe Hancock ◽  
Desmond G. Hunt ◽  
John L. Ivy ◽  
Lawrence J. Mandarino
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Acute Exercise ◽  
Citrate Synthase ◽  
Mapk Pathway ◽  
Insulin Response ◽  
Mitogen Activated Protein Kinase ◽  
Zucker Rats ◽  
Obese Zucker Rats ◽  
Ribosomal S6 Kinase

Acute exercise and training increase insulin action in skeletal muscle, but the mechanism responsible for this effect is unknown. Activation of the insulin receptor initiates signaling through both the phosphatidylinositol (PI) 3-kinase and the mitogen-activated protein kinase [MAPK, also referred to as extracellular signal-regulated kinases (ERK1/2)] pathways. Acute exercise has no effect on the PI3-kinase pathway signaling elements but does activate the MAPK pathway, which may play a role in the adaptation of muscle to exercise. It is unknown whether training produces a chronic effect on basal activity or insulin response of the MAPK pathway. The present study was undertaken to determine whether exercise training improves the activity of the MAPK pathway or its response to insulin in obese Zucker rats, a well-characterized model of insulin resistance. To accomplish this, obese Zucker rats were studied by using the hindlimb perfusion method with or without 7 wk of treadmill training. Activation of the MAPK pathway was determined in gastrocnemius muscles exposed in situ to insulin. Compared with lean Zucker rats, untrained obese Zucker rats had reduced basal and insulin-stimulated activities of ERK2 and its downstream target p90 ribosomal S6 kinase (RSK2). Seven weeks of training significantly increased basal and insulin-stimulated ERK2 and RSK2 activities, as well as insulin stimulation of MAPK kinase activity. This effect was maintained for at least 96 h in the case of ERK2. The training-induced increase in basal ERK2 activity was correlated with the increase in citrate synthase activity. Therefore, 7 wk of training increases basal and insulin-stimulated ERK2 activity. The increase in basal ERK2 activity may be related to the response of muscle to training.

THE EFFECT OF EXERCISE TRAINING ON SKELETAL MUSCLE GLUCOSE UPTAKE AND TRANSPORT

1992 ◽  
Vol 24 (Supplement) ◽  
pp. S141
Author(s):  
G. J. Etgen ◽  
E. A. Gulve ◽  
J. O. Holloszy ◽  
J. L. Ivy
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Glucose Uptake ◽  
Skeletal Muscle Glucose Uptake ◽  
Uptake And Transport

scholarly journals Chronic renin inhibition with aliskiren improves glucose tolerance, insulin sensitivity, and skeletal muscle glucose transport activity in obese Zucker rats

2012 ◽  
Vol 302 (1) ◽  
pp. R137-R142 ◽  
Author(s):  
Elizabeth M. Marchionne ◽  
Maggie K. Diamond-Stanic ◽  
Mujalin Prasonnarong ◽  
Erik J. Henriksen
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Glucose Transport ◽  
Insulin Action ◽  
Whole Body ◽  
Zucker Rats ◽  
Obese Zucker Rats ◽  
Renin Inhibition

We have demonstrated previously that overactivity of the renin-angiotensin system (RAS) is associated with whole body and skeletal muscle insulin resistance in obese Zucker ( fa/fa) rats. Moreover, this obesity-associated insulin resistance is reduced by treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor (type 1) blockers. However, it is currently unknown whether specific inhibition of renin itself, the rate-limiting step in RAS functionality, improves insulin action in obesity-associated insulin resistance. Therefore, the present study assessed the effect of chronic, selective renin inhibition using aliskiren on glucose tolerance, whole body insulin sensitivity, and insulin action on the glucose transport system in skeletal muscle of obese Zucker rats. Obese Zucker rats were treated for 21 days with either vehicle or aliskiren (50 mg/kg body wt ip). Renin inhibition was associated with a significant lowering (10%, P < 0.05) of resting systolic blood pressure and induced reductions in fasting plasma glucose (11%) and free fatty acids (46%) and homeostatic model assessment for insulin resistance (13%). Glucose tolerance (glucose area under the curve) and whole body insulin sensitivity (inverse of the glucose-insulin index) during an oral glucose tolerance test were improved by 15% and 16%, respectively, following chronic renin inhibition. Moreover, insulin-stimulated glucose transport activity in isolated soleus muscle of renin inhibitor-treated animals was increased by 36% and was associated with a 2.2-fold greater Akt Ser473 phosphorylation. These data provide evidence that chronic selective inhibition of renin activity leads to improvements in glucose tolerance and whole body insulin sensitivity in the insulin-resistant obese Zucker rat. Importantly, chronic renin inhibition is associated with upregulation of insulin action on skeletal muscle glucose transport, and it may involve improved Akt signaling. These data support the strategy of targeting the RAS to improve both blood pressure regulation and insulin action in conditions of insulin resistance.

scholarly journals Exercise training improves muscle insulin resistance but not insulin receptor signaling in obese Zucker rats

2002 ◽  
Vol 92 (2) ◽  
pp. 736-744 ◽  
Author(s):  
Christine Y. Christ ◽  
Desmond Hunt ◽  
Joe Hancock ◽  
Rebeca Garcia-Macedo ◽  
Lawrence J. Mandarino ◽  
...  
Keyword(s):  
Exercise Training ◽  
Insulin Receptor ◽  
Glucose Uptake ◽  
Exercise Bout ◽  
Pi3 Kinase ◽  
Serine Phosphorylation ◽  
Zucker Rats ◽  
Receptor Signaling ◽  
Insulin Receptor Signaling ◽  
Obese Zucker Rats

Exercise training improves skeletal muscle insulin sensitivity in the obese Zucker rat. The purpose of this study was to investigate whether the improvement in insulin action in response to exercise training is associated with enhanced insulin receptor signaling. Obese Zucker rats were trained for 7 wk and studied by using the hindlimb-perfusion technique 24 h, 96 h, or 7 days after their last exercise training bout. Insulin-stimulated glucose uptake (traced with 2-deoxyglucose) was significantly reduced in untrained obese Zucker rats compared with lean controls (2.2 ± 0.17 vs. 5.4 ± 0.46 μmol · g−1 · h−1). Glucose uptake was normalized 24 h after the last exercise bout (4.9 ± 0.41 μmol · g−1 · h−1) and remained significantly elevated above the untrained obese Zucker rats for 7 days. However, exercise training did not increase insulin receptor or insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation, phosphatidylinositol 3-kinase (PI3-kinase) activity associated with IRS-1 or tyrosine phosphorylated immunoprecipitates, or Akt serine phosphorylation. These results are consistent with the hypothesis that, in obese Zucker rats, adaptations occur during training that lead to improved insulin-stimulated muscle glucose uptake without affecting insulin receptor signaling through the PI3-kinase pathway.

Effects of exercise training on skeletal muscle glucose uptake and transport

1993 ◽  
Vol 264 (3) ◽  
pp. C727-C733 ◽  
Author(s):  
G. J. Etgen ◽  
J. T. Brozinick ◽  
H. Y. Kang ◽  
J. L. Ivy
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Glucose Uptake ◽  
Protein Content ◽  
Glucose Transport ◽  
Exercise Session ◽  
Rat Skeletal Muscle ◽  
Glut 4 ◽  
Skeletal Muscle Glucose Uptake ◽  
Uptake And Transport

Exercise training increases the concentration of GLUT-4 protein in skeletal muscle that is associated with an increase in maximal insulin-stimulated glucose transport. The purpose of this study was to determine whether exercise training results in a long-lasting increase in insulin-stimulated glucose transport in rat skeletal muscle. Glucose uptake and skeletal muscle 3-O-methyl-D-glucose (3-MG) transport were determined during hindlimb perfusion in the presence of a maximally stimulating concentration of insulin (10 mU/ml). Hindlimb glucose uptake was approximately 29% above sedentary (Sed) levels in rats examined within 24 h (24H) of their last exercise session. However, when rats were examined 48 h (48H) after their last exercise session, hindlimb glucose uptake was not different from Sed levels. Maximal 3-MG transport was enhanced, above Sed levels, in red (RG; 72% increase) and white (WG; 44% increase) gastrocnemius and plantaris (Plan; 67% increase) muscles, but not soleus (Sol), of 24H rats. GLUT-4 protein content was significantly elevated in those muscles that exhibited enhanced 3-MG transport in 24H rats. GLUT-4 protein content was also elevated in RG, WG, and Plan of 48H rats and was not different from 24H rats. Despite the elevated GLUT-4 protein content, 3-MG transport in 48H rats was only slightly, although statistically not significantly, higher than in Sed rats. These results provide evidence that exercise training does not result in a persistent increase in skeletal muscle glucose uptake or transport, despite an increase in GLUT-4 protein content.

scholarly journals Obesity Downregulates MicroRNA-126 Inducing Capillary Rarefaction in Skeletal Muscle: Effects of Aerobic Exercise Training

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
João Lucas Penteado Gomes ◽  
Tiago Fernandes ◽  
Ursula Paula Reno Soci ◽  
André Casanova Silveira ◽  
Diego Lopes Mendes Barretti ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Therapeutic Strategy ◽  
Group Versus ◽  
Aerobic Exercise Training ◽  
Zucker Rats ◽  
Vegf Signaling ◽  
Capillary Rarefaction ◽  
Obese Zucker Rats ◽  
Vegf Signaling Pathway

Background.We investigated the effects of exercise training (ET) on miR-126 levels and skeletal muscle angiogenesis in obese Zucker rats.Results.Zucker rats were randomly assigned to sedentary and swimming-trained groups: lean sedentary (LS) and trained (LTR); obese sedentary (OB) and trained (OBTR). The OB group displayed capillary rarefaction compared with the LS group. In contrast, ET increased the capillary/fiber ratio by 38% in the LTR group and normalized capillary rarefaction in the OBTR group. VEGF, PI3K, and eNOS levels were reduced in the skeletal muscle of the OB group. ET normalized VEGF, PI3K, and eNOS levels in OBTR, contributing to vascular network homeostasis. PI3KR2 inhibits PI3K, a key mediator of the VEGF signaling pathway. Obesity decreased miR-126 and increased PI3KR2 levels compared with the LS group. However, ET normalized miR-126 levels in the OBTR group versus the LS group and decreased expression of PI3KR2.Conclusion.Our findings show that obesity leads to skeletal muscle capillary rarefaction, which is regulated by decreased miR-126 levels and increased PI3KR2. Inversely, ET normalizes miR-126 levels and VEGF signaling and should be considered an important therapeutic strategy for vascular disorders.

scholarly journals Simvastatin Impairs Glucose Homeostasis in Mice Depending on PGC-1α Skeletal Muscle Expression

Biomedicines ◽  
2020 ◽  
Vol 8 (9) ◽  
pp. 351
Author(s):  
Miljenko Valentin Panajatovic ◽  
François Singh ◽  
Stephan Krähenbühl ◽  
Jamal Bouitbir
Keyword(s):  
Skeletal Muscle ◽  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Glucose Homeostasis ◽  
Simvastatin Treatment ◽  
Skeletal Muscle Glucose Uptake ◽  
Skeletal Muscle Insulin Sensitivity ◽  
Glycogen Stores

Several studies showed an increased risk for diabetes with statin treatment. PGC-1α is an important regulator of muscle energy metabolism and mitochondrial biogenesis. Since statins impair skeletal muscle PGC-1α expression and reduced PGC-1α expression has been observed in diabetic patients, we investigated the possibility that skeletal muscle PGC1α expression influences the effect of simvastatin on muscle glucose metabolism. Mice with muscle PGC-1α knockout (KO) or PGC-1α overexpression (OE), and wild-type (WT) mice were investigated. Mice were treated orally for 3 weeks with simvastatin (5 mg/kg/day) and investigated by intraperitoneal glucose tolerance (iGTT), in vivo skeletal muscle glucose uptake, muscle glycogen content, and Glut4 and hexokinase mRNA and protein expression. Simvastatin impaired glucose metabolism in WT mice, as manifested by increased glucose blood concentrations during the iGTT, decreased skeletal muscle glucose uptake and glycogen stores. KO mice showed impaired glucose homeostasis with increased blood glucose concentrations during the iGTT already without simvastatin treatment and simvastatin induced a decrease in skeletal muscle glucose uptake. In OE mice, simvastatin treatment increased blood glucose and insulin concentrations during the iGTT, and increased skeletal muscle glucose uptake, glycogen stores, and Glut4 and hexokinase protein expression. In conclusion, simvastatin impaired skeletal muscle insulin sensitivity in WT mice, while KO mice exhibited impaired skeletal muscle insulin sensitivity already in the absence of simvastatin. In OE mice, simvastatin augmented muscular glucose uptake but impaired whole-body insulin sensitivity. Thus, simvastatin affected glucose homeostasis depending on PGC-1α expression.

scholarly journals Exercise Counterbalances Rho/ROCK2 Signaling Impairment in the Skeletal Muscle and Ameliorates Insulin Sensitivity in Obese Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Vitor R. Muñoz ◽  
Rafael C. Gaspar ◽  
Matheus B. Severino ◽  
Ana P. A. Macêdo ◽  
Fernando M. Simabuco ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Physical Exercise ◽  
Glucose Uptake ◽  
Molecular Mechanisms ◽  
Tyrosine Phosphatase ◽  
C2c12 Myotubes ◽  
Obese Mice ◽  
Skeletal Muscle Glucose Uptake ◽  
The Impact

Physical exercise is considered a fundamental strategy in improving insulin sensitivity and glucose uptake in skeletal muscle. However, the molecular mechanisms underlying this regulation, primarily on skeletal muscle glucose uptake, are not fully understood. Recent evidence has shown that Rho-kinase (ROCK) isoforms play a pivotal role in regulating skeletal muscle glucose uptake and systemic glucose homeostasis. The current study evaluated the effect of physical exercise on ROCK2 signaling in skeletal muscle of insulin-resistant obese animals. Physiological (ITT) and molecular analysis (immunoblotting, and RT-qPCR) were performed. The contents of RhoA and ROCK2 protein were decreased in skeletal muscle of obese mice compared to control mice but were restored to normal levels in response to physical exercise. The exercised animals also showed higher phosphorylation of insulin receptor substrate 1 (IRS1 Serine 632/635) and protein kinase B (Akt) in the skeletal muscle. However, phosphatase and tensin homolog (PTEN) and protein-tyrosine phosphatase-1B (PTP-1B), both inhibitory regulators for insulin action, were increased in obesity but decreased after exercise. The impact of ROCK2 action on muscle insulin signaling is further underscored by the fact that impaired IRS1 and Akt phosphorylation caused by palmitate in C2C12 myotubes was entirely restored by ROCK2 overexpression. These results suggest that the exercise-induced upregulation of RhoA-ROCK2 signaling in skeletal muscle is associated with increased systemic insulin sensitivity in obese mice and further implicate that muscle ROCK2 could be a potential target for treating obesity-linked metabolic disorders.

scholarly journals Exercise training reduces skeletal muscle membrane arachidonate in the obese (fa/fa) Zucker rat

1998 ◽  
Vol 85 (5) ◽  
pp. 1898-1902 ◽  
Author(s):  
Kerry J. Ayre ◽  
Stephen D. Phinney ◽  
Anna B. Tang ◽  
Judith S. Stern
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Exercise Training ◽  
Extensor Digitorum Longus ◽  
Extensor Digitorum ◽  
Zucker Rats ◽  
Muscle Membrane ◽  
Positive Effects ◽  
Fast Twitch ◽  
White Gastrocnemius

Compared with the lean ( Fa/−) genotype, obese ( fa/fa) Zucker rats have a relative deficiency of muscle phospholipid arachidonate, and skeletal muscle arachidonate in humans is positively correlated with insulin sensitivity. To assess the hypothesis that the positive effects of exercise training on insulin sensitivity are mediated by increased muscle arachidonate, we randomized 20 lean and 20 obese weanling male Zucker rats to sedentary or treadmill exercise groups. After 9 wk, fasting serum, three skeletal muscles (white gastrocnemius, soleus, and extensor digitorum longus), and heart were obtained. Fasting insulin was halved by exercise training in the obese rat. In white gastrocnemius and extensor digitorum longus (fast-twitch muscles), but not in soleus (a slow-twitch muscle) or heart, phospholipid arachidonate was lower in obese than in lean rats ( P < 0.001). In all muscles, exercise in the obese rats reduced arachidonate ( P < 0.03, by ANOVA contrast). We conclude that improved insulin sensitivity with exercise in the obese genotype is not mediated by increased muscle arachidonate and that reduced muscle arachidonate in obese Zucker rats is unique to fast-twitch muscles.

Chronic Exercise Training Increases Insulin Sensitivity in Obese Zucker Rats Potentially Via Hypothalamic Adiponectin Receptor 1

2006 ◽  
Vol 38 (Suppl 1) ◽  
pp. S39
Author(s):  
Amy L. Sindler ◽  
Sarah Morgan ◽  
Rafael A. Reyes ◽  
Jonathan M. Peterson ◽  
Jefferson C. Frisbee ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Exercise Training ◽  
Adiponectin Receptor ◽  
Zucker Rats ◽  
Chronic Exercise ◽  
Adiponectin Receptor 1 ◽  
Obese Zucker Rats
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