Induction of hepatic glycogenesis in the fetal rat.

We have performed an in vivo study to test the hypothesis that induction of fetal hepatic glycogenesis is stimulated by insulin and involves activation of protein phosphatase type-1. Control animals and the following two experimental groups were studied: maternal fasting for 48 h prior to term and chronic maternal hyperinsulinemia for 5 days prior to term. Maternal fasting led to decreased fetal hepatic glycogen content and fetal growth retardation. In contrast, no decrease in fetal hepatic glycogen content or fetal weight occurred with maternal hyperinsulinemia despite fetal hypoglycemia and fetal hypoinsulinemia. In neither model were fetal hepatic synthase phosphatase or phosphorylase phosphatase activities affected. In control fetuses, the appearance of hepatic glycogen from days 17 to 21 of gestation correlated with induction of glycogen synthase. Phosphorylase phosphatase and synthase phosphatase activities already were present on day 17 of gestation and changed little through term. However, phosphatase catalytic protein reactive with anti-phosphatase type-1 antibodies did increase approximately fivefold from day 18 to 21. In adult animals fasted for 48 h, 50% of hepatic glycogen synthase phosphatase activity was lost, whereas phosphorylase phosphatase activity was stimulated fourfold. The apparent size of protein phosphatase type-1 catalytic subunit as detected by Western immunoblotting was altered by fasting in the adult but not by substrate restriction (maternal fasting) in the fetus.(ABSTRACT TRUNCATED AT 250 WORDS)