PI 3-kinase activation is required for insulin stimulation of glucose transport into L6 myotubes.
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.
Berger
J
J
Department of Molecular Endocrinology, Merck Research Laboratories, Rahway, NJ 07065.
Hayes
N
N
Szalkowski
D M
DM
Zhang
B
B
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
D000730:Androstadienes; D007328:Insulin; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D005947:Glucose; D000077191:Wortmannin