PI 3-kinase activation is required for insulin stimulation of glucose transport into L6 myotubes

Biochem Biophys Res Commun. 1994 Nov 30;205(1):570-6. doi: 10.1006/bbrc.1994.2703.

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.

MeSH terms

  • Androstadienes / pharmacology
  • Animals
  • Biological Transport
  • Cell Line
  • Enzyme Activation
  • Glucose / metabolism*
  • Insulin / pharmacology*
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism
  • Phosphatidylinositol 3-Kinases
  • Phosphotransferases (Alcohol Group Acceptor) / antagonists & inhibitors
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Wortmannin

Substances

  • Androstadienes
  • Insulin
  • Phosphatidylinositol 3-Kinases
  • Phosphotransferases (Alcohol Group Acceptor)
  • Glucose
  • Wortmannin