title: PI 3-kinase activation is required for insulin stimulation of glucose transport into L6 myotubes.
abstract: Phosphatidylinositol 3-kinase (PI 3-kinase) is acutely stimulated by insulin but its role in regulating glucose metabolism is still not fully understood. Insulin acutely stimulates glucose transport into L6 myotubes approximately 2-fold, and activates PI 3-kinase activity 2 to 3-fold. Wortmannin, an inhibitor of PI 3-kinase, blocked insulin stimulation of 2-deoxyglucose transport into the myotubes in a time and dose-dependent manner. Inhibition was observed within 5 minutes and was complete by 30 minutes. The IC50 for this inhibition was approximately 10 nM; almost complete inhibition was observed at 100 nM. Similarly, insulin stimulation of PI 3-kinase activity was inhibited by wortmannin in a dose-dependent manner. The insulinmimetic vanadate activated hexose transport into the myotubes to more than 50% of the maximal level attained with insulin. Only approximately 60% of vanadate-activated glucose transport was inhibited by maximal wortmannin concentrations. It is concluded that insulin activation of PI 3-kinase is necessary for stimulation of glucose transport into L6 muscle cells. In contrast, vanadate appears to augment transport by acting upon PI 3-kinase-dependent and independent pathways.
authors.affiliation: Department of Molecular Endocrinology, Merck Research Laboratories, Rahway, NJ 07065.
authors.forename: J
authors.initials: J
authors.lastname: Berger
authors.forename: N
authors.initials: N
authors.lastname: Hayes
authors.forename: D M
authors.initials: DM
authors.lastname: Szalkowski
authors.forename: B
authors.initials: B
authors.lastname: Zhang
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D004789:Enzyme Activation; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D007328:Insulin; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D005947:Glucose; D000077191:Wortmannin