Effects of somatostatin on glucagon-stimulated glycogenolysis and gluconeogenesis in hepatocytes cultured in vitro

The effects of somatostatin (SS-14) on glycogenolysis and gluconeogenesis in rat hepatocytes cultured in vitro in a serum-free medium were investigated. Somatostatin (122 nmol 1^-1) did not significantly change the basal glucose production with or without pyruvate (10 mmol 1^-1). Glucagon strongly (over 100%) increased the glucose production in hepatocytes incubated in a medium supplemented with 10 mmol 1^-1 pyruvate. This increase in glucose production is the result of increased rates of gluconeogenesis and glycogenolysis. Somatostatin partially inhibited the glucagon stimulated increase in glucose production. Glucagon also significantly increased the glucose production in a glucose-free medium without pyruvate, which resulted from an increase of glycogenolysis. Somatostatin did not inhibit the increase in glucose production in these conditions. After a 4 h ‘fast’, glycogen in hepatocytes fell to a very low level. Glucose production was minimal. After the addition of pyruvate, there was a increase in gluconeogenesis and glucose production. Glucagon stimulated the rate of gluconeogenesis. Somatostatin completely inhibited this glucagon-stimulated increase in gluconeogenesis.