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

Christine Y. Christ, Desmond Hunt, Joe Hancock, Rebeca Garcia-Macedo, Lawrence J. Mandarino, John L. Ivy

Research output: Contribution to journalArticlepeer-review

76 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)736-744
Number of pages9
JournalJournal of Applied Physiology
Issue number2
StatePublished - 2002
Externally publishedYes


  • Glucose uptake
  • Insulin receptor substrate-1
  • Phosphatidylinositol 3-kinase
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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