GLUCAGON INCREASES GLUTAMINE UPTAKE WITHOUT AFFECTING GLUTAMINE RELEASE IN HUMANS

Glucagon causes transient hyperglycemia and persistent hypoaminoacidem ia, but the mechanisms of this action are unclear. To address this que stion, the present study measured the effects of glucagon on glucose, leucine, phenylalanine, and glutamine kinetics. Seven healthy subjects each underwent three pancreatic clamp studies (octreotide 30 ng/kg/mi n, insulin 0.15 mU/kg/min, and glucagon 1.4 ng/kg/min) lasting 7 hours . During the last 3.5 hours of the studies, glucagon infusion was eith er unchanged (study 0) or increased to 4 and 7 ng/kg/min (studies 1 an d 2). The higher glucagon infusion rates increased the glucagon concen tration by 50% and 100%, respectively. [6,6-H-2(2)]glucose, [2-N-15]gl utamine, H-2(5)-phenylalanine, and H-2(3)-leucine were infused to quan tify the respective fluxes. Glucagon transiently increased glucose con centrations by stimulating glucose production, which peaked in 15 minu tes to 3.82 +/- 0.36 and 4.21 +/- 0.33 mg/kg/min in studies 1 and 2 an d then returned to the postabsorptive levels. Glucagon decreased the g lutamine concentration (-10% +/- 2% and -22% +/- 2% in studies 1 and 2 v study 0, P < .05), because glutamine uptake became greater than glu tamine release (balance from -1.9 +/- 0.9 in study 0 to -8.1 +/- 1.1 a nd -13.6 +/- 1.0 mu mol/kg/h in studies 1 and 2, P < .01). Glucagon de creased the leucine concentration (-11% +/- 3% in study 2 v study 0, P < .02) and caused a small increment in proteolysis (+6% in study 2 v study 0, P < .01) that was related to the decrement in glutamine conce ntrations. Phenylalanine kinetics were not significantly affected. The se results show that glucagon promotes the uptake of gluconeogenic sub strates but does not increase their release, suggesting that glucagon- induced hyperglycemia is short-lived because glucagon fails to provide more fuel for gluconeogenesis, The small increase in proteolysis and the depletion of circulating glutamine prove that physiologic hyperglu cagonemia can contribute to protein catabolism. Copyright (C) 1998 by W.B. Saunders Company.