Effects of vasopressin on fructose and glycogen metabolism in hepatocytes from fed and fasted rats

Abstract

Hepatocytes were isolated from fed and 24-hr-fasted rats and incubated with lactate plus pyruvate in the presence and absence of 30 m m glucose. The effects of fructose and/ or vasopressin (ADH) on the activities of glycogen synthase and phosphorylase were examined and correlated with their effects on glycogen content. Effects of glucose and vasopressin on the metabolism of [U- 14C]fructose were also studied. ADH-stimulated net glycogenolysis in hepatocytes from fed rats was inhibited by each fructose concentration studied. In the presence of glucose, lactate, and pyruvate, low concentrations of fructose (up to 5 m m) markedly increased hepatocyte glycogen content, but high concentrations (20–40 m m) prevented net glycogen synthesis. In the presence or absence of glucose or of ADH, incubation of hepatocytes with 2 m m fructose generally caused either no change or a slight activation of both glycogen synthase and phosphorylase. About 80% of the radioactivity initially present as [U- 14C]fructose was incorporated after 80 min into glucose and about 1% into glycogen in hepatocytes from both fed and fasted rats. Addition of glucose reduced the amount of radioactivity incorporated into glucose to 65%, and increased that into glycogen about fivefold. ADH had no effect on the percentage of radioactivity incorporated into glucose, CO 2, or anionic metabolites, but it decreased the percentage of radioactivity incorporated into glycogen by about fivefold. Thus the only observed effect of ADH on [U- 14C]fructose metabolism in hepatocytes from fed or fasted rats in the presence or absence of 30 m m glucose was to decrease deposition of radioactive glycogen, an effect consistent with the observed ADH-mediated inactivation of glycogen synthase and activation of phosphorylase.