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 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.

The gastroenteroinsular response to glucose ingestion during postexercise recovery

“…This reduced or delayed insulin response has also been reported by other investigators (21,25,27,32,33,37,Fig. 3.…”

“…These data suggest that VIP may play an important glucoregulatory role when glucose is ingested during the immediate postexercise recovery period. insulin resistance; gut peptides; exercise performance; carbohydrate THE IMMEDIATE POSTEXERCISE PERIOD appears to be associated with mild reversible insulin resistance, which is characterized by an attenuated insulin response and an increased glucose response to oral glucose (10,21,25,27,33,37,39,43). The physiological basis for the increased glucose response has been shown to be partly a function of greater release of glucose from the splanchnic tissues (20,30,39).…”

Exercise training increases insulin-stimulated glucose disposal and GLUT4 (SLC2A4) protein content in patients with type 2 diabetes

“…In the immediate aftermath of exercise, IRS1-associated PI3K activity [30] and GLUT4 protein content [31] are unaltered. The muscle glycogen concentration and glycogen synthase activity after exercise contribute to the regulation of glucose transport and disposal in an insulin-independent manner [32].…”

The Muscle-specific Protein Phosphatase PP1G/RGL(GM) Is Essential for Activation of Glycogen Synthase by Exercise

“…GS has been shown to be regulated differentially in skeletal muscle by insulin and contractions during in vitro and in vivo studies (43)(44)(45), with contractions and exercise resulting in a prolonged, substantially greater activation compared with maximal insulin treatment. This suggests that contractions may utilize a separate signaling pathway from insulin to activate GS in response to contractions.…”