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

Abstract

The counter-regulatory hormones, including glucagon, may be involved in the generation of postoperative negative nitrogen balance. We examined the influence of glucagon on whole body and forearm muscle protein kinetics, determined by L-[1-13C, 15N]leucine, in two matched groups of healthy fasting subjects. In one study somatostatin alone was infused continuously (0.12 mg h-1) and in another with glucagon (0.04 mg h-1) to generate insulin resistance. Somatostatin infusion increased leucine oxidation (P less than 0.05) and reduced the negative protein balance (P less than 0.01) across the forearm; the 15 per cent decrease in protein breakdown was not significant. Whole body leucine kinetics showed increased flux (P less than 0.05) and synthesis (P less than 0.01) but reduced oxidation (P less than 0.05). Hyperglucagonaemia caused a threefold enhancement of leucine oxidation (P less than 0.02), while the negative protein balance further increased (P less than 0.05) across the forearm. Whole body leucine flux was unchanged; oxidation increased (P less than 0.01) and synthesis decreased (P less than 0.01). These studies confirm that physiological hyperglucagonaemia during insulin resistance is catabolic in the short-term and indicates, for the first time, that glucagon may influence muscle protein metabolism acutely in man. We suggest that therapeutic manoeuvres designed to reduce glucagon levels after surgery may ameliorate protein kinetic abnormalities.