Effects of glucagon on renal and hepatic glutamine gluconeogenesis in normal postabsorptive humans

Glutamine is an important gluconeogenic amino acid in postabsorptive humans. To assess the effect of glucagon on renal and hepatic glutamine gluconeogenesis, we infused six normal healthy postabsorptive subjects with glucagon at a rate chosen to produce circulating glucagon concentrations found during hypoglycemia and, using a combination of isotopic and net balance techniques, determined the systemic, renal, and hepatic 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 micromol x kg(-1) x min(-1), respectively, to 0.61 +/- 0.04 (P = .002) and 0.31 +/- 0.03 micromol x kg(-1) x min(-1) (P = .001), respectively, whereas renal glutamine gluconeogenesis was unchanged (from 0.33 +/- 0.03 to 0.30 +/- 0.04 micromol x kg(-1) x 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 = .003). Glucagon had no effect on the renal net balance, fractional extraction, or uptake and release of either glucose or glutamine. We thus conclude that glucagon stimulates glutamine gluconeogenesis in normal postabsorptive humans, predominantly due to an increase in hepatic glutamine conversion to glucose. Thus, under certain conditions such as counterregulation of hypoglycemia, the liver may be an important site of glutamine gluconeogenesis.