Effect of hyperglucagonemia on whole-body leucine metabolism in immature pigs before and during a meal

Leucine metabolism was measured isotopically in 12 immature female pigs to assess the effect of acute hyperglucagonemia on leucine kinetics in both the fed and fasting states. After an overnight fast, immature pigs were infused with alpha-[3H]ketoisocaproate and [14C]leucine. After a 2-h equilibration period, an infusion of either saline or 7 pg.kg-1.min-1 of glucagon was begun, which increased plasma glucagon from approximately 140 to approximately 640 pg/ml and doubled the insulin concentrations. Two hours later, pigs were fed small meals to which [5,5,5-2H3]leucine was added to trace absorption. By subtracting absorption from total leucine flux, an estimate of endogenous proteolysis during the meal was made. In the fasting state, glucagon increased proteolysis, relative to controls, by approximately 20% (P less than 0.05) and increased oxidation by approximately 50% (P less than 0.05). No significant glucagon-related changes in any other flux parameters occurred in the fasting state. Ingestion of the meals caused oxidation to increase 41% in control animals, whereas in glucagon-infused animals, oxidation increased 84% (P less than 0.05 control vs. glucagon response to meal). Additionally, animals infused with glucagon suppressed endogenous proteolysis 43% after the meal compared with a 55% decrease in control animals (P less than 0.05 basal period vs. fed period). These data indicate that glucagon stimulates whole-body proteolysis in both the fasting and fed states.