SummaryThe present study was designed to investigate glucose metabolism in the postmature fetus and newborn. In the fetus, the decreased hepatic glycogen content together with the decrease by the same percentage of total hepatic glycogen radioactivity from directly injected [6-3H]glucose demonstrate that fetal glycogenolysis occurs during prolonged gestation. Moreover, fetal glycogen synthesis as tested byin vivo[6-3H]glucose incorporation experiments is inhibited.In vivoexperiments with [14C]lactate are consistent with gluconeogenesis, being inactive in the postmature fetus as well as in the normal-term fetus. During the first hr after delivery, ourin vivodata about conversion of [14C]lactate to glucose show that the gluconeogenic pathway is not functioning in spite of very high phosphoenolpyruvate carboxykinase activity in the postmature. By 3 hr postpartum, the phosphoenolpyruvate carboxykinase activity, the blood lactate level, the percentage of conversion, and the rate of gluconeogenesis are very elevated in the postmatures as compared to the term neonates. By 6 hr postpartum, despite maintained phosphoenolpyruvate carboxykinase activity, gluconeogenic rate becomes very weak in postmatures kept fasting. This is the time characterized by a profound hypoglycemia. In contrast, fed postmature neonates exhibit normal blood glucose levels by 6 and 12 hr postpartum as a result of sustained rate of gluconeogenesis.SpeculationIn utero hepatic glycogenolysis of the postmature rat leads to impaired capacity to cope with neonatal fasting. Gluconeogenic pathway, as measured under normal blood oxygenation of the mother, is not operating in the postmature as well as in the term fetus.