Glucagon increases glutamine uptake without affecting glutamine release in humans

doi:10.1016/S0026-0495(98)90036-1

Metabolism

Volume 47, Issue 6, June 1998, Pages 713-723

https://doi.org/10.1016/S0026-0495(98)90036-1 Get rights and content

Abstract

Glucagon causes transient hyperglycemia and persistent hypoaminoacidemia, but the mechanisms of this action are unclear. To address this question, 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/min, 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 either unchanged (study 0) or increased to 4 and 7 ng/kg/min (studies 1 and 2). The higher glucagon infusion rates increased the glucagon concentration by 50% and 100%, respectively. [6,6-²H₂]glucose, [2-¹⁵N]glutamine, ²H₅-phenylalanine, and ²H₃-leucine were infused to quantify the respective fluxes. Glucagon transiently increased glucose concentrations by stimulating glucose production, which peaked in 15 minutes to 3.82 ± 0.36 and 4.21 ± 0.33 mg/kg/min in studies 1 and 2 and then returned to the postabsorptive levels. Glucagon decreased the glutamine concentration (−10% ± 2% and −22% ± 2% in studies 1 and 2 v study 0, P < .05), because glutamine uptake became greater than glutamine release (balance from −1.9 ± 0.9 in study 0 to −8.1 ± 1.1 and −13.6 ± 1.0 μmol/kg/h in studies 1 and 2, P < .01). Glucagon decreased 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 concentrations. Phenylalanine kinetics were not significantly affected. These results show that glucagon promotes the uptake of gluconeogenic substrates 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 hyperglucagonemia can contribute to protein catabolism.

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Citation Excerpt :
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^☆: Supported in part by research grants from the National Institutes of Health (DK-38429, RR-02635-13, RR-00047, and RR-00109).

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Glucagon increases glutamine uptake without affecting glutamine release in humans☆

Abstract

Metabolism

Biochem Biophys Res Commun

Clin Nutr

FEBS Lett

FEBS Lett

Anal Biochem

Anal Biochem

Life Sci

Metabolism

Metabolism

Biochem Biophys Res Commun

Adv Enzyme Regul

J Biol Chem

Metabolism

Lancet

Differential time course of glucagon's effect on glycogenolysis and gluconeogenesis in the conscious dog

Diabetes

Contribution of hepatic glycogenolysis to glucose production in humans in response to a physiological increase in plasma glucagon concentration

Diabetes

Contributions of gluconeogenesis and glycogenolysis during glucose counterregulation in normal humans

Am J Physiol

Plasma amino acid kinetics during acute states of glucagon deficiency and excess in healthy adults

Am J Physiol

Glucagon-induced autophagy and proteolysis in rat liver: Mediation by selective deprivation of intracellular amino acids

Influence of glucagon on protein and leucine metabolism: A study in fasting man with induced insulin resistance

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Hyperglucagonemia stimulates phenylalanine oxidation in humans

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Bradykinin attenuates glucagon-induced leucine oxidation in humans

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