Pancreastatin inhibits insulin-stimulated glycogen synthesis but not glycolysis in rat hepatocytes.

The effect of rat pancreastatin on glycogen synthesis and glycolysis rate was studied in insulin-stimulated rat hepatocytes. We have determined the incorporation of [U-14C]glucose into glycogen as a measurement of the rate of glycogen synthesis; and the production of lactate as a measurement of the rate of glycolysis. Rat pancreastatin by itself did not affect either the rate of glycogen synthesis or glycolysis in rat hepatocytes from 6 h fasted rats. However, pancreastatin inhibited about 45% the insulin-stimulated glycogen synthesis whereas it enhanced the rate of glycolysis of insulin-stimulated hepatocytes about 25%. These effects were found to be dependent on pancreastatin concentration 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 decreased the rate of glycogen synthesis in a wide range of insulin concentrations (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 possible mechanisms involved in insulin resistance.