title: 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.
authors.affiliation: Noll Physiological Research Center and the General Clinical Research Center, Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: O'Gorman
authors.forename: L F
authors.initials: LF
authors.lastname: Del Aguila
authors.forename: D L
authors.initials: DL
authors.lastname: Williamson
authors.forename: R K
authors.initials: RK
authors.lastname: Krishnan
authors.forename: J P
authors.initials: JP
authors.lastname: Kirwan
mesh_terms: D000328:Adult; D001706:Biopsy; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D002153:Calorimetry, Indirect; D004040:Dietary Carbohydrates; D002149:Energy Intake; D015444:Exercise / Q000502:physiology*; D005215:Fasting; D006006:Glycogen Synthase / Q000378:metabolism*; D006801:Humans; D006946:Hyperinsulinism; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins; D000078790:Insulin Secretion; D008297:Male; D018482:Muscle, Skeletal / Q000166:cytology / Q000201:enzymology*; D010101:Oxygen Consumption; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D005082:Physical Exertion / Q000502:physiology*; D011187:Posture; D012420:Running
chemical_list: D001786:Blood Glucose; D004040:Dietary Carbohydrates; C526292:IRS1 protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D010750:Phosphoproteins; D006006:Glycogen Synthase; D019869:Phosphatidylinositol 3-Kinases