Reversal of diet-induced insulin resistance with a single bout of exercise in the rat: the role of PTP1B and IRS-1 serine phosphorylation

J Physiol. 2006 Dec 15;577(Pt 3):997-1007. doi: 10.1113/jphysiol.2006.120006. Epub 2006 Sep 28.


Lifestyle interventions including exercise programmes are cornerstones in the prevention of obesity-related diabetes. In this study, we demonstrate that a single bout of exercise inhibits high-fat diet-induced insulin resistance. Diet-induced obesity (DIO) increased the expression and activity of the protein tyrosine phosphatase 1B (PTP1B) and attenuated insulin signalling in gastrocnemius muscle of rats, a phenomenon which was reversed by a single session of exercise. In addition, DIO was observed to lead to serine phosphorylation of insulin receptor substrate 1 (IRS-1), which was also reversed by exercise in muscle in parallel with a reduction in c-Jun N-terminal kinase (JNK) activity. Thus, acute exercise increased the insulin sensitivity during high-fat feeding in obese rats. Overall, these results provide new insights into the mechanism by which exercise restores insulin sensitivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dietary Fats / administration & dosage*
  • Dose-Response Relationship, Drug
  • I-kappa B Proteins / antagonists & inhibitors
  • Insulin / metabolism
  • Insulin Receptor Substrate Proteins
  • Insulin Resistance*
  • JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Male
  • Muscle, Skeletal / metabolism
  • Obesity / etiology
  • Obesity / metabolism
  • Obesity / physiopathology*
  • Phosphoproteins / chemistry*
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Physical Conditioning, Animal*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases / metabolism*
  • Rats
  • Rats, Wistar
  • Recovery of Function
  • Serine / metabolism
  • Signal Transduction
  • Swimming


  • Dietary Fats
  • I-kappa B Proteins
  • Insulin
  • Insulin Receptor Substrate Proteins
  • Irs1 protein, rat
  • Phosphoproteins
  • Serine
  • JNK Mitogen-Activated Protein Kinases
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases
  • Ptpn1 protein, rat