Insulin but not progesterone promotes the biosynthesis of glycogen in Xenopus laevis oocytes: implications on the control of glycogen synthase by phosphorylation, dephosphorylation.

Insulin, the well-known hypoglycemic hormone, mimics progesterone in promoting the resumption of meiosis within the oocyte of Xenopus laevis. Both hormones exert their action through the inhibition of protein kinases and the activation of protein phosphatases. Because glycogen synthase is an enzyme regulated by a kinases/phosphatases cascade, we investigated the effect of insulin and progesterone on the regulation of glycogen synthesis and glycogen synthase throughout the oogenesis of Xenopus laevis oocytes. In this framework the maximal activity of synthase "a" is concomitant with the vitellogenic period characterized by a drastic increase in the amount of glycogen. Oocyte glycogen synthase is inhibited by cAMP-dependent phosphorylation and stimulated by 20 mM Mg2+. The magnesium effect is inhibited by mu molar concentrations of okadaic acid and suggests that oocyte glycogen synthase is activated by dephosphorylation achieved by protein phosphatase-1. The okadaic acid effect is itself thwarted by the specific inhibitor of protein kinase A, confirming the role of this kinase in the regulation of glycogen synthase. Finally, working on intact ripe oocytes, we showed that insulin but not progesterone increases glycogen synthesis and glycogen synthase "a" activity and lowers the rates of phosphorylation, especially in the glycogen-bound proteins.