INSULIN ACTIVATES PROTEIN-KINASE-B, INHIBITS GLYCOGEN-SYNTHASE KINASE-3 AND ACTIVATES GLYCOGEN-SYNTHASE BY RAPAMYCIN-INSENSITIVE PATHWAYS IN SKELETAL-MUSCLE AND ADIPOSE-TISSUE

Insulin stimulated protein kinase B alpha (PKB alpha) more than 10-fol d and decreased glycogen synthase kinase-3 (GSK3) activity by 50+/-10% in skeletal muscle and adipocytes. Rapamycin did not prevent the acti vation of PKB, inhibition of GSK3 or stimulation of glycogen synthase up to 5 min. Thus rapamycin-insensitive pathways mediate the acute eff ect of insulin on glycogen synthase in the major insulin-responsive ti ssues, The small and very transient effects of EGF on phosphatidylinos itol (3,4,5)P-3 PKB alpha and GSK3 in adipocytes, compared to the stro ng and sustained effects of insulin, explains why EGF does not stimula te glucose uptake or glycogen synthesis in adipocytes. (C) 1997 Federa tion of European Biochemical Societies.