INSULIN-STIMULATED GLYCOGEN-SYNTHESIS IN ISOLATED RAT HEPATOCYTES - EFFECT OF PROTEIN-KINASE INHIBITORS

Glycogen synthesis was studied in rat hepatocytes isolated by EDTA per fusion. Insulin induced a one and a half to twofold increase in glucos e incorporation into glycogen. Insulin stimulated glycogen synthesis w as inhibited by the phosphatidylinositol 3-kinase inhibitors wortmanni n (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 s imilar to 40 mu M). Wortmannin was without appreciable effect on non-i nsulin stimulated glycogen synthesis, while LY 294002 and PD 98059 als o 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 Elsevi er Science Inc.