Hormonal regulation of glycogen metabolism in neonatal rat liver

The development of active and inactive phosphorylase was determined in rat liver during the perinatal period. No inactive form could be found in tissues from animals less than 19 days gestation or older than the 5th postnatal day. The regulation of phosphorylase in organ cultures of fetal rat liver was examined. None of the agents examined [glucagon, insulin or dibutyryl cyclic AMP (6 N,2' O dibutyryladenosine 3':5' cyclic monophosphate)] changed the amount of phosphorylase activity. Glycogen concentration in these explants were nevertheless decreased more than 2 fold by 4 hr of incubation with glucagon or dibutyryl cyclic AMP. Incubation with insulin for 4 hr increased the glycogen content twofold. Glycogen synthetase activity was examined in these explants. I form activity (without glucose 6 phosphate) was found to decrease by a factor of 2 after 4 hr incubation with dibutyryl cyclic AMP, whereas I + D activity (with glucose 6 phosphate) remained nearly constant. Incubation for 4 hr with insulin increased I form activity threefold, with only a slight increase in I + D activity. When explants were incubated with insulin followed by addition of dibutyryl cyclic AMP, the effects of insulin on glycogen concentration and glycogen synthetase activity were reversed. These results indicate that the regulation of glycogen synthesis may be the major factor in the hormonal control of glycogen metabolism in neonatal rat liver.