Control of Gluconeogenesis and of Enzymes of Glycogen Metabolism in Isolated Rat Ilepatocytes

Hepatocytes isolated from the livers of fed rats were used for a cQmparative study of the effects of phenylephrine, vasopressin and glucagon on gluconeogenesis and Qn enzymes of glycogen metabolism. When hepatocytes were incubated in the presence of Ca2 , phanylephrine stimulated gluconeogenesis from pyruvate less than did glucagon, but, in contrast with this hormone, it did not affect the activities of protein kinase and pyruvate kintse, nor the concentration of phosphoenolpyruvate, and it did not decrease the release of 3H20 from [6-3H]glucose. The effects of vasopressin were similar to those of phenylephrine. Gluconeogenesis from fructose was also stimulated by phenylephrine and, more markedly, by glucagon at the expense ofthe conversion of fructose into lactate. Insulin was able to antagonize the stim'ulatory effect of phenylephrine on gluconeogenesis from pyruvate. When Ca2+ was removqd from the incubation medium, phenylephrine still stimulated gluconeogenesis from pyruvate, but it also caused an activation of protein kinase and an inactivation of pyruvate kinase; accordingly, the concentration ofphosphoenolpyruvate was increased, and, in contrast, vasopressin had no effect on all these parameters. The property of phenylephrine to cause the activation of glycogen phosphorylase was decreased by glucose or by the absence of Ca2+; it was abolished when these two conditions were combined. Glycogen synthase was inactivated by phenylephrine in the presence or the absence of Ca2+, although presumably by different mechanisms.