Perinatal onset of hepatic gluconeogenesis in the lamb

Hepatic gluconeogenesis does not occur in the unstressed fetal sheep. After birth, in addition to glycogenolysis, the newborn lamb must eventually initiate gluconeogenesis to maintain glucose homeostasis. The regulation and time course of this transition have not been defined. We studied six animals in an acute preparation before and after delivery to determine hepatic lactate and glucose uptake, hepatic gluconeogenesis from lactate, and plasma catecholamine and cortisol concentrations. After a priming dose, continuous infusion of [14C]lactate provided tracer substrate for calculations of gluconeogenesis in the fetus and then for ten hours after delivery in the newborn lamb. The radionuclide-labelled microsphere method was used to measure hepatic blood flow. Appreciable gluconeogenesis was not present during the fetal period. Following delivery, the newborn lambs began to produce significant quantities of glucose from lactate at 6 h of age (1.37 +/- 0.84 mg.min-1.100 g-1 min-1 x 100 g-1 liver), when gluconeogenesis from lactate accounted for 22% of hepatic glucose output. Despite the onset of gluconeogenesis, postnatal lambs had blood glucose concentrations that remained less than fetal levels of 23.4 +/- 12.1 mg/dl for the duration of the 10-h study. Plasma norepinephrine concentration was 1380 +/- 1145 pg/ml in the fetus and fell by 2 h after birth. Plasma epinephrine concentrations were highest at 15 min after birth (205 +/- 262 pg/ml), but remained quite low for the remainder of the study. Plasma cortisol concentrations did not vary over the course of study, ranging from 40 to 50 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)