Insulin stimulated glycogen synthesis in isolated rat hepatocytes: Effect of protein kinase inhibitors

Glycogen synthesis was studied in rat hepatocytes isolated by EDTA perfusion. Insulin induced a one and a half to twofold increase in glucose incorporation into glycogen. Insulin stimulated glycogen synthesis was inhibited by the phosphatidylinositol 3-kinase inhibitors wortmannin (IC50 similar to 40 nM) and LY 294002 (IC50 similar to 20 mu M) and the mitogen-activated protein kinase kinase inhibitor PD 98059 (IC50 similar to 40 mu M). Wortmannin was without appreciable effect on non-insulin stimulated glycogen synthesis, while LY 294002 and PD 98059 also inhibited the non insulin stimulated glycogen synthesis. Rapamycin, an inhibitor of p70 ribosomal protein-S6 kinase, was without effect on glycogen synthesis regardless of insulin stimulation. (C) 1997 Elsevier Science Inc.