Insulin and exercise differentially regulate PI3-kinase and glycogen synthase in human skeletal muscle

J Appl Physiol (1985). 2000 Oct;89(4):1412-9. doi: 10.1152/jappl.2000.89.4.1412.


The purpose of this study was to determine the separate and combined effects of exercise and insulin on the activation of phosphatidylinositol 3-kinase (PI3-kinase) and glycogen synthase in human skeletal muscle in vivo. Seven healthy men performed three trials in random order. The trials included 1) ingestion of 2 g/kg body wt carbohydrate in a 10% solution (CHO); 2) 75 min of semirecumbent cycling exercise at 75% of peak O(2) consumption; followed by 5 x 1-min maximal sprints (Ex); and 3) Ex, immediately followed by ingestion of the carbohydrate solution (ExCHO). Plasma glucose and insulin were increased (P < 0.05) at 15 and 30 (Post-15 and Post-30) min after the trial during CHO and ExCHO, although insulin was lower for ExCHO. Hyperinsulinemia during recovery in CHO and ExCHO led to an increase (P < 0.001) in PI3-kinase activity at Post-30 compared with basal, although the increase was lower (P < 0. 004) for ExCHO. Furthermore, PI3-kinase activity was suppressed (P < 0.02) immediately after exercise (Post-0) during Ex and ExCHO. Area under the insulin response curve for all trials was positively associated with PI3-kinase activity (r = 0.66, P < 0.001). Glycogen synthase activity did not increase during CHO but was increased (P < 0.05) at Post-0 and Post-30 during Ex and ExCHO. Ingestion of the drink increased (P < 0.05) carbohydrate oxidation during CHO and ExCHO, although the increase after ExCHO was lower (P < 0.05) than CHO. Carbohydrate oxidation was directly correlated with PI3-kinase activity for all trials (r = 0.63, P < 0.001). In conclusion, under resting conditions, ingestion of a carbohydrate solution led to activation of the PI3-kinase pathway and oxidation of the carbohydrate. However, when carbohydrate was ingested after intense exercise, the PI3-kinase response was attenuated and glycogen synthase activity was augmented, thus facilitating nonoxidative metabolism or storage of the carbohydrate. Activation of glycogen synthase was independent of PI3-kinase.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Biopsy
  • Blood Glucose / metabolism
  • Body Mass Index
  • Calorimetry, Indirect
  • Dietary Carbohydrates*
  • Energy Intake
  • Exercise / physiology*
  • Fasting
  • Glycogen Synthase / metabolism*
  • Humans
  • Hyperinsulinism
  • Insulin / blood
  • Insulin / metabolism*
  • Insulin Receptor Substrate Proteins
  • Insulin Secretion
  • Male
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / enzymology*
  • Oxygen Consumption
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphoproteins / metabolism
  • Physical Exertion / physiology*
  • Posture
  • Running


  • Blood Glucose
  • Dietary Carbohydrates
  • IRS1 protein, human
  • Insulin
  • Insulin Receptor Substrate Proteins
  • Phosphoproteins
  • Glycogen Synthase
  • Phosphatidylinositol 3-Kinases