EFFECTS OF GLUCAGON ON RENAL AND HEPATIC GLUTAMINE GLUCONEOGENESIS INNORMAL POSTABSORPTIVE HUMANS

Glutamine is an important gluconeogenic amino acid in postabsorptive h umans. To assess the effect of glucagon on renal and hepatic glutamine gluconeogenesis, we infused six normal healthy postabsorptive subject s with glucagon at a rate chosen to produce circulating glucagon conce ntrations found during hypoglycemia and, using a combination of isotop ic and net balance techniques, determined the systemic, renal, and hep atic glucose release and renal and hepatic production of glucose from glutamine. Infusion of glucagon increased systemic and hepatic glucose release (both P < .02), but had no effect on renal glucose release (P = .26). Systemic and hepatic glutamine gluconeogenesis increased from 0.45 +/- 0.3 and 0.11 +/- 0.02 mu mol.kg(-1).min(-1), respectively, t o 0.61 +/- 0.04 (P = .002) and 0.31 +/- 0.03 mu mol.kg(-1).min(-1) (P = .001), respectively, whereas renal glutamine gluconeogenesis was unc hanged (from 0.33 +/- 0.03 to 0.30 +/- 0.04 mu mol.kg(-1).min(-1), P = .20). The hepatic contribution to systemic glutamine gluconeogenesis increased from 25.2% +/- 6.2% to 51.6% +/- 5.5% (P = .002), while that of the kidney decreased from 74.8% +/- 6.2% to 48.4% +/- 5.5% (P = .0 03). Glucagon had no effect on the renal net balance, fractional extra ction, or uptake and release of either glucose or glutamine. We thus c onclude that glucagon stimulates glutamine gluconeogenesis in normal p ostabsorptive humans, predominantly due to an increase in hepatic glut amine conversion to glucose. Thus, under certain conditions such as co unterregulation of hypoglycemia, the liver may be an important site of glutamine gluconeogenesis. Copyright (C) 1998 by W.B. Saunders Compan y.