Hyperglucagonemia and the immediate fate of dietary leucine: A kinetic study in humans☆

Abstract 

The possible role of glucagon in determining the fate of dietary absorbed amino acids within the splanchnic bed was investigated in five healthy male volunteers. A kinetic study was performed involving a continuous 240-minute infusion of l-[5,5,5-²H₃]leucine and d-[6,6-²H₂]glucose by vein, while l-[1-¹³C]leucine was infused by a feeding tube into the duodenum (intragut [IG]) along with a constant intravenous (IV) infusion of somatotropin release-inhibitory factor (SRIF) combined with insulin, growth hormone, and glucagon. In random order, glucagon was infused at a rate of 0.4 ng · kg⁻¹ · min⁻¹ in one experiment and 1.2 ng · kg⁻¹ · min⁻¹ in the other experiment, while insulin and growth hormone were kept at constant serum levels, respectively, 37 ± 13 pmol · L⁻¹ and 5 ± 0.2 μg · L⁻¹. The diet was provided as an l-amino acid solution including 60 μmol · kg⁻¹ · h⁻¹ leucine without fat and carbohydrate. During the higher rate of glucagon infusion, there was an increase in plasma glucagon and glucose concentrations, glucose flux, and net dietary leucine release into the periphery from the splanchnic bed. Splanchnic removal and uptake of leucine were decreased with increased glucagon infusion. There were no statistical differences in the plasma leucine level and IV and IG leucine fluxes at the two glucagon levels, although leucine metabolic clearance increased (0.74 v 0.85 L · kg⁻¹ · h⁻¹, P = .08) in the case of glucagon excess. Plasma glucose increased with glucagon excess and was negatively correlated (P < .05) with the plasma leucine level (r = −.348) and IV (r = −.459) or I.G. (r = −.359) leucine fluxes. The negative correlation between plasma glucagon and leucine levels was also significant (r = −.684). No significant correlation was found between dietary leucine splanchnic removal and glucose, glucagon, or leucine plasma concentrations. We conclude that glucagon in excess has only a small quantitative effect on the overall handling of dietary leucine, and hypothesize that more leucine is exported to the peripheral tissues under these hormonal conditions.

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