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 Bα (PKBα) 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 PKBα 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.