PANCREASTATIN INHIBITS INSULIN-STIMULATED GLYCOGEN-SYNTHESIS BUT NOT GLYCOLYSIS IN RAT HEPATOCYTES

The effect of rat pancreastatin on glycogen synthesis and glycolysis r ate was studied in insulin-stimulated rat hepatocytes. We have determi ned the incorporation of [U-C-14]glucose into glycogen as a measuremen t of the rate of glycogen synthesis; and the production of lactate as a measurement of the rate of glycolysis. Rat pancreastatin by itself d id not affect either the rate of glycogen synthesis or glycolysis in r at hepatocytes from 6 h fasted rats. However, pancreastatin inhibited about 45% the insulin-stimulated glycogen synthesis whereas it enhance d the rate of glycolysis of insulin-stimulated hepatocytes about 25%. These effects were found to be dependent on pancreastatin concentratio n from 10(-11) M to 10(-7) M. Maximal effect was achieved at 10(-8) M and the half-maximal effect was observed at 0.3 nM. Pancreastatin decr eased the rate of glycogen synthesis in a wide range of insulin concen trations (10(-12)-10(-8) M). However, the effect on insulin-stimulated glycolysis was only observed at high concentrations of pancreastatin and insulin. These results suggest a role of pancreastatin in the poss ible mechanisms involved in insulin resistance.