Effect of vasoactive intestinal polypeptide on glycogen metabolism in rat hepatocytes

Abstract

The effects of vasoactive intestinal polypeptide (VIP) on several enzymes of glycogen metabolism in rat hepatocytes were compared with those of glucagon and of vasopressin (ADH). VIP caused phosphorylase activation and glycogenolysis in hepatocytes from fed rats. In hepatocytes from fasted rats incubated with glucose, lactate, and pyruvate, VIP inhibited net glycogen deposition, inactivated glycogen synthase, and activated phosphorylase. VIP was about 100-fold less potent than glucagon and 1,000-fold less potent than ADH in causing activation of phosphorylase. The ability of VIP to activate phosphorylase was not altered by chelation of the calcium in the medium. The half maximal effective doses of VIP for both phosphorylase activation and stimulation of glycogenolysis were 10-30 nM. Treatment with VIP, ADH, or glucagon did not decrease phosphorylase phosphatase activity. Each of these hormones, however, lengthened the lag time before synthase phosphatase activity was expressed in vitro. Other gut hormones tested did not affect hepatocyte glycogen metabolism. These results do not support the concept of physiologic control of hepatic glycogen metabolism by VIP or by other gut hormones.