Control of gluconeogenesis and of enzymes of glycogen metabolism in isolated rat hepatocytes. A parallel study of the effect of phenylephrine and of glucagon

Abstract

Hepatocytes isolated from the livers of fed rats were used for a comparative study of the effects of phenylephrine, vasopressin and glucagon on gluconeogenesis and on enzymes of glycogen metabolism. When hepatocytes were incubated in the presence of Ca2+, phenylephrine stimulated gluconeogenesis from pyruvate less than did glucagon, but unlike glucagon it did not affect the activities of protein kinase and pyruvate kinase, nor the concentration of phosphoenolpyruvate, and it did not decrease the release of 3H2O from [6-3H]glucose. The effects of vasopressin were similar to those of phenylephrine. Gluconeogenesis from fructose was also stimulated by phenylephrine and glucagon at the expense of the conversion of fructose into lactate. Insulin was able to antagonize the stimulatory effect of phenylephrine on gluconeogenesis from pyruvate. When Ca2+ was removed from the incubation medium, phenylephrine still stimulated gluconeogenesis from pyruvate, but it also cuased an activation of protein kinase and an inactivation of pyruvate kinase; the concentration of phosphoenolpyruvate was increased, and vasopressin had no effect on all these parameters. The ability of phenylephrine to cause the activation of glycogen phosphorylase was decreased by glucose or by the absence of Ca2+; it was abolished when these 2 conditions were combined. Glycogen synthase was inactivated by phenylephrine in the presence or the absence of Ca2+, although presumably by different mechanisms.