(2, 28) have shown that certain adult glucagon secretogogues such as arginine or epinephrine could produce a significant fetal hyperglucagonemia. Recent work (13) suggests that elevation in fetal glucagon concentration may accompany prolonged maternal fasting.The physiologic function of fetal hyperglucagonemia is also open to question. A hyperglycemic response to pharmacologic injection has been suggested in in vivo preparations (6). In order to clarify the role of glucagon as a possible fetal metabolic regulatory hormone, we utilized the chronically catheterized fetal sheep as our model. Varying degrees of hyperglucagonemia were induced and alterations in fetal glucagon, insulin, glucose and ketone concentrations as well as umbilical glucose and ketone uptakes then noted.
Summary SpeculationThe fetus in late gestation may respond to substrate deprivation by secretion of glucagon. If so, a modest but significant hyperglycemia would result, presumably the result of acute fetal glycogenolysis. The acute fetal metabolic adaptation to maternal starvation, however, if modified by glucagon, does not include utilization of ketones as alternate substrates.Acute glucagon injections were performed in chronically catheterized fetal lambs in late gestation to assess the fetal metabolic response to exogenous glucagon infusion. Glucagon dosages between 1 p,g/kg and 1 mg/kg induced significant fetal hyperglycemia by 15-30 min postinjection, with peak glucose values 130-180% of control. Increasing responsivity to the same dose/kg was noted to parallel increasing gestational age. In selected preparations in which umbilical venous catheters were implanted, glucagon injection caused an acute fall in the glucose/oxygen quotient and net umbilical glucose consumption. The fall in glucose consumption to 8% of control values occurred within 15 min of injection and suggests acute fetal glucose excretion, probably secondary to hepatic glycogenolysis. Glucagon injection in the neonatal lamb caused qualitatively similar increases in plasma glucose concentration but the quantitative responses were considerably greater. No change in fetal ,B-hydroxybutyrate (,B-ORD) concentration was noted after injection; nor did the fetal uptake or excretion of this ketone change. The neonatal ,B-ORD concentration was significantly different (P < 0.001) from fetal concentrations and did rise 14% above control after glucagon injection; thus, elevation of plasma glucagon in the fetus causes an acute hyperglycemia but, unlike the adult, does not induce a significant ketogenesis.Experimental design. Eleven pregnant ewes between 118-149 days of gestation were studied (Table 1). Term gestation in the sheep is 147 days. All but two had singleton fetuses. Intravenous sodium pentobarbital and spinal anesthesia were administered to each animal preoperatively. Polyvinyl catheters were then placed in a fetal pedal artery and vein as well as the maternal femoral artery for purposes of sampling and infusion. In five of the fetal lambs umbilical venous catheters were als...