Insulin-stimulated insulin receptor substrate-2-associated phosphatidylinositol 3-kinase activity is enhanced in human skeletal muscle after exercise

Metabolism. 2006 Aug;55(8):1046-52. doi: 10.1016/j.metabol.2006.03.016.


Exercise increases skeletal muscle insulin action but the underlying mechanisms mediating this are equivocal. In mouse skeletal muscle, prior exercise enhances insulin-stimulated insulin receptor substrate-2 (IRS-2) signaling (Diabetes 2002;51:479-83), but it is unknown if this also occurs in humans. Hyperinsulinemic-euglycemic clamps were performed on 7 untrained males at rest and immediately after 60 minutes of cycling exercise at approximately 75% Vo2peak. Muscle biopsies were obtained at basal, immediately after exercise, and at 30 and 120 minutes of hyperinsulinemia. Insulin infusion increased (P < .05) insulin receptor tyrosine phosphorylation similarly in both the rest and exercise trials. Under resting conditions, insulin infusion resulted in a small, but non-statistically significant increase in IRS-2-associated phosphatidylinositol 3 (PI 3)-kinase activity over basal levels. Exercise per se decreased (P < .05) IRS-2-associated PI 3-kinase activity. After exercise, insulin-stimulated IRS-2-associated PI 3-kinase activity tended to increase at 30 minutes and further increased (P < .05) at 120 minutes when compared with the resting trial. Insulin increased (P < .05) Akt Ser473 and GSK-3alpha/beta Ser21/Ser9 phosphorylation in both trials, with the response tending to be higher in the exercise trial. In conclusion, in the immediate period after an acute bout of exercise, insulin-stimulated IRS-2 signaling is enhanced in human skeletal muscle.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose / metabolism
  • Cross-Over Studies
  • Double-Blind Method
  • Exercise / physiology*
  • Exercise Test
  • Fatty Acids, Nonesterified / blood
  • Glucose Clamp Technique
  • Glycogen / metabolism
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • Humans
  • Immunoblotting
  • Insulin / blood
  • Insulin Receptor Substrate Proteins
  • Intracellular Signaling Peptides and Proteins
  • Lactic Acid / blood
  • Male
  • Muscle, Skeletal / enzymology*
  • Muscle, Skeletal / metabolism
  • Oncogene Protein v-akt / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphoproteins / physiology*
  • Phosphorylation
  • Signal Transduction / physiology


  • Blood Glucose
  • Fatty Acids, Nonesterified
  • IRS2 protein, human
  • Insulin
  • Insulin Receptor Substrate Proteins
  • Intracellular Signaling Peptides and Proteins
  • Irs2 protein, mouse
  • Phosphoproteins
  • Lactic Acid
  • Glycogen
  • Phosphatidylinositol 3-Kinases
  • Glycogen Synthase Kinase 3 beta
  • Oncogene Protein v-akt
  • Glycogen Synthase Kinase 3
  • glycogen synthase kinase 3 alpha