Abstract
The influence of glucagon, choleragen, and the adrenal glucocorticoids on glycogenolysis in primary cultures of adult rat liver parenchymal cells has been studied. Both glucagon and choleragen caused a twofold to threefold stimulation of glucose production from endogenous reserves of glycogen. The effect of glucagon on glucose production was noted at the earliest time point examined and the stimulation of glucose production was preceded by an elevation of cyclic AMP. Choleragen did not produce a significant stimulation of glucose production until 45 minutes after addition of the agent. Choleragen effects on glucose production were preceded by an elevation of cyclic AMP, but in contrast with glucagon, choleragen did not significantly elevate cyclic AMP until 30 minutes after addition to the culture. One ng of choleragen per ml of medium was sufficient to produce an effect on glucose production. Glucagonโ or choleragenโtreated cultures mobilized glycogen more rapidly than did untreated cultures incubated in glucoseโfree medium. In addition, both agents produced a stong inhibition of lactate production. Thus, the stimulation of glucose production by these agents was partially due to increased glycogen mobilization and partially due to redirection of carbon units from glycolysis. That glucose production in the hepatocytes is regulated in part by a cyclic AMPโdependent mechanism is strongly supported by the observation that both agents elevate cyclic AMP and cause an increase in glucose production and inhibition of lactate production. The possibility that the glucocorticoids participated in the regulation of glycogenolysis either in a direct or indirect (permissive) fashion was assessed. It was found that when the direct effect of the glucocorticoids on glycogenesis was taken into account, the glucocorticoids had no direct effects on glycogenolysis, nor did they alter the stimulation of glycogenolysis by glucagon or choleragen.