Insulin activates protein kinase B, inhibits glycogen synthase kinase-3 and activates glycogen synthase by rapamycin-insensitive pathways in skeletal muscle and adipose tissue

FEBS Lett. 1997 Apr 7;406(1-2):211-5. doi: 10.1016/s0014-5793(97)00240-8.

Abstract

Insulin stimulated protein kinase B alpha (PKB alpha) more than 10-fold and decreased glycogen synthase kinase-3 (GSK3) activity by 50 +/- 10% in skeletal muscle and adipocytes. Rapamycin did not prevent the activation of PKB, inhibition of GSK3 or stimulation of glycogen synthase up to 5 min. Thus rapamycin-insensitive pathways mediate the acute effect of insulin on glycogen synthase in the major insulin-responsive tissues. The small and very transient effects of EGF on phosphatidylinositol (3,4,5)P3 PKB alpha and GSK3 in adipocytes, compared to the strong and sustained effects of insulin, explains why EGF does not stimulate glucose uptake or glycogen synthesis in adipocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / drug effects*
  • Adipose Tissue / enzymology
  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors*
  • Cells, Cultured
  • Enzyme Activation
  • Epidermal Growth Factor / pharmacology
  • Glycogen Synthase / metabolism*
  • Glycogen Synthase Kinase 3
  • Glycogen Synthase Kinases
  • Insulin / pharmacology*
  • Male
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / enzymology
  • Phosphatidylinositol Phosphates / metabolism
  • Polyenes / pharmacology
  • Protein-Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-akt
  • Rats
  • Rats, Wistar
  • Sirolimus

Substances

  • Insulin
  • Phosphatidylinositol Phosphates
  • Polyenes
  • Proto-Oncogene Proteins
  • phosphatidylinositol 3,4,5-triphosphate
  • Epidermal Growth Factor
  • Glycogen Synthase
  • Glycogen Synthase Kinases
  • Akt1 protein, rat
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Glycogen Synthase Kinase 3
  • Sirolimus