Glycogen synthase, synthase phosphatase, and phosphorylase response to glucose in somatostatin-pretreated intact rats

The response of the glycogen synthase and phosphorylase systems of the liver to intravenous glucose in the presence and absence of short term somatostatin blockade of insulin secretion was determined in fed and 20 h fasted rats. These enzyme systems regulate glycogen synthesis and degradation, respectively. In the presence of somatostatin, intravenous glucose (1.0 g/kg) promptly (5 min) increased the proportion of synthase in the I (active) form, and the increase was similar to that in animals that had not received somatostatin. In the same animals, phosphorylase a also was decreased, and the decrease was similar in all groups. When a smaller dose of glucose (250 mg/kg) was used that only modestly increased plasma glucose (139 mg/dl) and produced a less than maximal synthase response, insulin (1 U/kg) did not potentiate glucose activation of synthase either in the presence or absence of somatostatin. Phosphorylase a did not change significantly in any group. Glucose, in both the presence and absence of somatostatin, also rapidly (2 min) converted synthase phosphatase from a form inhibited by EDTA to a form not inhibited by EDTA. These data indicate that the synthase and phosphorylase systems in vivo respond primarily to a rise in plasma glucose and not to a simultaneous elevation in plasma insulin. Thus, glucose is regulating its own storage as glycogen in the liver. The effect of glucose on the synthase may be mediated through a conversion of the synthase phosphatase to a form that is not dependent on divalent cation for activity. This form presumably is more active in vivo.