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

Abstract

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 O2 consumption; followed by 5 × 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.