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Contraction of insulin-resistant muscle normalizes insulin action in association with increased mitochondrial activity and fatty acid catabolism.

Publication ,  Journal Article
Thyfault, JP; Cree, MG; Zheng, D; Zwetsloot, JJ; Tapscott, EB; Koves, TR; Ilkayeva, O; Wolfe, RR; Muoio, DM; Dohm, GL
Published in: Am J Physiol Cell Physiol
February 2007

Acute exercise can reverse muscle insulin resistance, but the mechanism(s) of action are unknown. With the use of a hindlimb perfusion model, we have found that acute contraction restores insulin-stimulated glucose uptake in muscle of obese Zucker rats to levels witnessed in lean controls. Previous reports have suggested that obesity-related insulin resistance stems from lipid oversupply and tissue accumulation of toxic lipid intermediates that impair insulin signaling. We reasoned that contraction might activate hydrolysis and oxidation of intramuscular lipids, thus alleviating "lipotoxicity" and priming the muscle for enhanced insulin action. Indeed, analysis of mitochondrial-derived acyl-carnitine esters suggested that contraction caused robust increases in beta-oxidative flux and mitochondrial oxidation. As predicted, contraction decreased intramuscular triacylglycerol content; however, diacylglycerol and long chain acyl-CoAs, lipid intermediates presumed to trigger insulin resistance, were either unchanged or increased. In muscles from obese animals, insulin-stimulated tyrosine phosphorylation of the insulin receptor and insulin receptor substrate-1 remained impaired after contraction, whereas phosphorylation of the downstream signaling protein, AS160, was partially restored. These results suggest that acute exercise enables diabetic muscle to circumvent upstream defects in insulin signal transduction via mechanisms that are more tightly coupled to increased mitochondrial energy metabolism than the lowering of diacylglycerol and long chain acyl-CoA.

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Published In

Am J Physiol Cell Physiol

DOI

ISSN

0363-6143

Publication Date

February 2007

Volume

292

Issue

2

Start / End Page

C729 / C739

Location

United States

Related Subject Headings

  • Triglycerides
  • Signal Transduction
  • Rats, Zucker
  • Rats
  • Protein Serine-Threonine Kinases
  • Physiology
  • Phosphorylation
  • Muscle, Skeletal
  • Muscle Contraction
  • Multienzyme Complexes
 

Citation

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Chicago
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MLA
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Thyfault, J. P., Cree, M. G., Zheng, D., Zwetsloot, J. J., Tapscott, E. B., Koves, T. R., … Dohm, G. L. (2007). Contraction of insulin-resistant muscle normalizes insulin action in association with increased mitochondrial activity and fatty acid catabolism. Am J Physiol Cell Physiol, 292(2), C729–C739. https://doi.org/10.1152/ajpcell.00311.2006
Thyfault, John P., Melanie G. Cree, Donghai Zheng, Jennifer J. Zwetsloot, Edward B. Tapscott, Timothy R. Koves, Olga Ilkayeva, Robert R. Wolfe, Deborah M. Muoio, and G Lynis Dohm. “Contraction of insulin-resistant muscle normalizes insulin action in association with increased mitochondrial activity and fatty acid catabolism.Am J Physiol Cell Physiol 292, no. 2 (February 2007): C729–39. https://doi.org/10.1152/ajpcell.00311.2006.
Thyfault JP, Cree MG, Zheng D, Zwetsloot JJ, Tapscott EB, Koves TR, et al. Contraction of insulin-resistant muscle normalizes insulin action in association with increased mitochondrial activity and fatty acid catabolism. Am J Physiol Cell Physiol. 2007 Feb;292(2):C729–39.
Thyfault, John P., et al. “Contraction of insulin-resistant muscle normalizes insulin action in association with increased mitochondrial activity and fatty acid catabolism.Am J Physiol Cell Physiol, vol. 292, no. 2, Feb. 2007, pp. C729–39. Pubmed, doi:10.1152/ajpcell.00311.2006.
Thyfault JP, Cree MG, Zheng D, Zwetsloot JJ, Tapscott EB, Koves TR, Ilkayeva O, Wolfe RR, Muoio DM, Dohm GL. Contraction of insulin-resistant muscle normalizes insulin action in association with increased mitochondrial activity and fatty acid catabolism. Am J Physiol Cell Physiol. 2007 Feb;292(2):C729–C739.

Published In

Am J Physiol Cell Physiol

DOI

ISSN

0363-6143

Publication Date

February 2007

Volume

292

Issue

2

Start / End Page

C729 / C739

Location

United States

Related Subject Headings

  • Triglycerides
  • Signal Transduction
  • Rats, Zucker
  • Rats
  • Protein Serine-Threonine Kinases
  • Physiology
  • Phosphorylation
  • Muscle, Skeletal
  • Muscle Contraction
  • Multienzyme Complexes