3D analysis of capillary network in skeletal muscle of obese insulin-resistant mice

Best known as chaperones, heat shock proteins (HSPs) also have roles in cell signalling and regulation of metabolism. Rodent studies demonstrate that heat treatment, transgenic overexpression and pharmacological induction of HSP72 prevent high-fat diet-induced glucose intolerance and skeletal muscle insulin resistance. Overexpression of skeletal muscle HSP72 in mice has been shown to increase endurance running capacity nearly twofold and increase mitochondrial content by 50%. A positive correlation between HSP72 mRNA expression and mitochondrial enzyme activity has been observed in human skeletal muscle, and HSP72 expression is markedly decreased in skeletal muscle of insulin resistant and type 2 diabetic patients. In addition, decreased levels of HSP72 correlate with insulin resistance and non-alcoholic fatty liver disease progression in livers from obese patients. These data suggest the targeted induction of HSPs could be a therapeutic approach for preventing metabolic disease by maintaining the body's natural stress response. Exercise elicits a number of metabolic adaptations and is a powerful tool in the prevention and treatment of insulin resistance. Exercise training is also a stimulus for increased HSP expression. Although the underlying mechanism(s) for exercise-induced HSP expression are currently unknown, the HSP response may be critical for the beneficial metabolic effects of exercise. Exercise-induced extracellular HSP release may also contribute to metabolic homeostasis by actively restoring HSP72 content in insulin resistant tissues containing low endogenous levels of HSPs. This article is part of the theme issue ‘Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective’.

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Voluntary Wheel Running Selectively Augments Insulin-Stimulated Vasodilation in Arterioles from White Skeletal Muscle of Insulin-Resistant Rats

Microcirculation ◽

10.1111/j.1549-8719.2012.00210.x ◽

2012 ◽

Vol 19 (8) ◽

pp. 729-738 ◽

Cited By ~ 22

Author(s):

Catherine R. Mikus ◽

Bruno T. Roseguini ◽

Grace M. Uptergrove ◽

E. Matthew Morris ◽

Randy Scott Rector ◽

...

Keyword(s):

Skeletal Muscle ◽

Wheel Running ◽

Voluntary Wheel Running ◽

Insulin Resistant ◽

Voluntary Wheel

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Localization of Rate-Limiting Defect for Glucose Disposal in Skeletal Muscle of Insulin-Resistant Type I Diabetic Patients

Diabetes ◽

10.2337/diab.39.2.157 ◽

1990 ◽

Vol 39 (2) ◽

pp. 157-167 ◽

Cited By ~ 51

Author(s):

H. Yki-Jarvinen ◽

K. Sahlin ◽

J. M. Ren ◽

V. A. Koivisto

Keyword(s):

Skeletal Muscle ◽

Glucose Disposal ◽

Diabetic Patients ◽

Type I ◽

Insulin Resistant ◽

Rate Limiting

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Insulin Signaling and Glucose Transport in Insulin Resistant Skeletal Muscle

Advances in Experimental Medicine and Biology - Skeletal Muscle Metabolism in Exercise and Diabetes ◽

10.1007/978-1-4899-1928-1_7 ◽

1998 ◽

pp. 73-85 ◽

Cited By ~ 16

Author(s):

Dana Galuska ◽

Jeff Ryder ◽

Yuichi Kawano ◽

Maureen J. Charron ◽

Juleen R. Zierath

Keyword(s):

Skeletal Muscle ◽

Glucose Transport ◽

Insulin Signaling ◽

Insulin Resistant

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Isomer-specific actions of conjugated linoleic acid on muscle glucose transport in the obese Zucker rat

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00013.2003 ◽

2003 ◽

Vol 285 (1) ◽

pp. E98-E105 ◽

Cited By ~ 52

Author(s):

Erik J. Henriksen ◽

Mary K. Teachey ◽

Zachary C. Taylor ◽

Stephan Jacob ◽

Arne Ptock ◽

...

Keyword(s):

Oxidative Stress ◽

Skeletal Muscle ◽

Glucose Tolerance ◽

Glucose Transport ◽

Zucker Rat ◽

Transport Activity ◽

Insulin Resistant ◽

Obese Zucker Rat ◽

Cla Isomers ◽

Muscle Glucose Transport

The fatty acid-conjugated linoleic acid (CLA) enhances glucose tolerance and insulin action on skeletal muscle glucose transport in rodent models of insulin resistance. However, no study has directly compared the metabolic effects of the two primary CLA isomers, cis-9, trans-11-CLA (c9,t11-CLA) and trans-10, cis-12-CLA (t10,c12-CLA). Therefore, we assessed the effects of a 50:50 mixture of these two CLA isomers (M-CLA) and of preparations enriched in either c9,t11-CLA (76% enriched) or t10,c12-CLA (90% enriched) on glucose tolerance and insulin-stimulated glucose transport in skeletal muscle of the insulin-resistant obese Zucker ( fa/ fa) rat. Animals were treated daily by gavage with either vehicle (corn oil), M-CLA, c9,t11-CLA, or t10,c12-CLA (all CLA treatments at 1.5 g total CLA/kg body wt) for 21 consecutive days. During an oral glucose tolerance test, glucose responses were reduced ( P < 0.05) by 10 and 16%, respectively, in the M-CLA and t10,c12-CLA animals, respectively, whereas insulin responses were diminished by 21 and 19% in these same groups. There were no significant alterations in these responses in the c9,t11-CLA group. Insulin-mediated glucose transport activity was enhanced by M-CLA treatment in both type I soleus (32%) and type IIb epitrochlearis (58%) muscles and by 36 and 48%, respectively, with t10,c12-CLA. In the soleus, these increases were associated with decreases in protein carbonyls (index of oxidative stress, r = -0.616, P = 0.0038) and intramuscular triglycerides ( r = -0.631, P = 0.0028). Treatment with c9,t11-CLA was without effect on these variables. These results suggest that the ability of CLA treatment to improve glucose tolerance and insulin-stimulated glucose transport activity in insulin-resistant skeletal muscle of the obese Zucker rat are associated with a reduction in oxidative stress and muscle lipid levels and can be specifically ascribed to the actions of the t10,c12 isomer. In the obese Zucker rat, the c9,t11 isomer of CLA is metabolically neutral.

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