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.