THE ROLE OF GLUCAGON IN THE CONTROL OF PROTEIN AND AMINO-ACID-METABOLISM IN-VIVO

The relative contribution of hyperglucagonemia to the mechanisms of nitrogen loss during catabolic states has not been clearly established. The present study examines the independent effect of physiologic elevations of plasma glucagon on whole-body protein kinetics, as well as on net amino acid balance across the liver and gastrointestinal tract tissues, in conscious Is-hour-fasted dogs (n = 7). Each study consisted of a 120-minute equilibration period, a 30-minute basal period, and a 150-minute experimental period. Leucine kinetics were measured using L-[1-C-14]leucine. Pancreatic hormones were maintained by infusing intravenous somatostatin (0.8 mu g/kg.min), intraportal insulin (275 mu U/kg.min), and intraportal glucagon (0.65 ng/kg.min basally and 2.5 experimentally). Dextrose was infused to maintain plasma glucose constant (14.1 +/- 0.3 mu mol/L), thereby providing a consistent metabolic steady state for the study of protein and amino acid metabolism. In the experimental period, plasma glucagon was fourfold basal levels (112 +/- 10 v 32 +/- 6 pg/mL), whereas plasma insulin remained stable (mean, lO +/- 1 mu U/mL). Hepatic glucose production was increased 30%, but leucine rates of appearance ([R(a)] proteolysis), oxidative disappearance (R(d)), and nonoxidative R(d) (protein synthesis) were not altered during the experimental period. Furthermore, the net release of amino acids by the gastrointestinal tract was not increased by glucagon. However, uptake and extraction of amino acids by the liver were increased, resulting in a 17% decrease in total plasma amino acids. Therefore, these data indicate that the major role of elevated glucagon in vivo is not to increase the rate of whole-body proteolysis, but rather is to facilitate hepatic uptake of amino acids, thereby leading to an increase in glucose production.