Influence of exogenous glucagon on fetal glucose metabolism and ketone production.

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 microgram/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 beta-hydroxybutyrate (beta-OHB) concentration was noted after injection; nor did the fetal uptake or excretion of this ketone change. The neonatal beta-OHB concentration was significantly different (P less than 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.