Regulation of hepatic glycogen synthesis during fetal development: roles of hydrocortisone, insulin, and insulin receptors.
In fetal rat liver in utero, an increase in glycogen and the glycogen synthetic enzyme glycogen synthetase (EC 2.4.1.11) occurs between gestational days 17 and 19. We used an organ culture system for finding the stimulus for increased enzyme activity and defining the relationship of this increase to glycogen synthesis. In fetal-liver explants from an earlier period (gestational day 16), hydrocortisone causes an elevation in total glycogen synthetase activity. This effect, which can be blocked by actinomycin D, is strikingly similar in time course and magnitude to the normal increase in utero. However, in order for glycogen synthesis to proceed after hydrocortisone increases glycogen synthetase levels, insulin is required. Unlike hydrocortisone, insulin does not increase total glycogen synthetase; it appears to act by converting the b or phospho form of synthetase to the a or dephospho form. Insulin alone does not stimulate glycogen synthesis in explants from 16-day fetal liver, although no defect in insulin binding was demonstrable. These findings support the hypothesis that the increase in liver-glycogen synthesis during the last trimester requires glucocorticoids for the developmental induction of glycogen synthetase and insulin for activation of the enzyme.
D000818:Animals; D001665:Binding Sites; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004790:Enzyme Induction; D005865:Gestational Age; D006003:Glycogen / Q000096:biosynthesis*; D006006:Glycogen Synthase / Q000378:metabolism; D006854:Hydrocortisone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D008099:Liver / Q000196:embryology* / Q000378:metabolism; D009924:Organ Culture Techniques; D011284:Pregnenolone / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D011956:Receptors, Cell Surface; D013268:Stimulation, Chemical
D007328:Insulin; D007457:Iodine Radioisotopes; D011956:Receptors, Cell Surface; D003609:Dactinomycin; D011374:Progesterone; D011284:Pregnenolone; D003907:Dexamethasone; D006003:Glycogen; D006006:Glycogen Synthase; D006854:Hydrocortisone