title: Insulin-stimulated insulin receptor substrate-2-associated phosphatidylinositol 3-kinase activity is enhanced in human skeletal muscle after exercise.
abstract: 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.
authors.affiliation: Center for Physical Activity and Nutrition (C-PAN), School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria 3125, Australia. kirsten.howlett@deakin.edu.au
authors.forename: Kirsten F
authors.initials: KF
authors.lastname: Howlett
authors.forename: Kei
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Haiyan
authors.initials: H
authors.lastname: Yu
authors.forename: Laurie J
authors.initials: LJ
authors.lastname: Goodyear
authors.forename: Mark
authors.initials: M
authors.lastname: Hargreaves
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D018592:Cross-Over Studies; D004311:Double-Blind Method; D015444:Exercise / Q000502:physiology*; D005080:Exercise Test; D005230:Fatty Acids, Nonesterified / Q000097:blood; D015309:Glucose Clamp Technique; D006003:Glycogen / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D015151:Immunoblotting; D007328:Insulin / Q000097:blood; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D019344:Lactic Acid / Q000097:blood; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010750:Phosphoproteins / Q000502:physiology*; D010766:Phosphorylation; D015398:Signal Transduction / Q000502:physiology
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; C526297:IRS2 protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; C526298:Irs2 protein, mouse; D010750:Phosphoproteins; D019344:Lactic Acid; D006003:Glycogen; D019869:Phosphatidylinositol 3-Kinases; D000071679:Glycogen Synthase Kinase 3 beta; D051058:Oncogene Protein v-akt; D038362:Glycogen Synthase Kinase 3; C448021:glycogen synthase kinase 3 alpha