The effects of glucagon on protein metabolism in normal man

Plasma glucagon rises after major injury and could act to increase gluconeogenesis and ureagenesis in the post-traumatic state. This study documents the effect of prolonged glucagon infusion on ureagenesis and nitrogen excretion, as well as possible sources of the increased ureagenesis, in normal man. Four healthy men fasted for 6 days during intravenous infusion of glucose (750 gm/day), establishing a steady state of minimal ureagenesis. Glucagon (1 mg/day) then was added to the infusion for 5 days. Glucose alone was given for the final 2 days. Forearm muscle flux of metabolites was determined by standard arterial-deep venous sampling and capacitance plethysmography. Glucagon concentration was suppressed during glucose infusion (11 ± 13 pg/ml) and rose to levels seen in subjects with major trauma during glucagon infusion (669 ± 138 pg/ml). Glucose infusion stabilized urine nitrogen excretion at 1.54 ± 0.42 gm of N/sq m/day. Nitrogen excretion increased to 2.40 ± 0.53 gm of N/sq m/day with glucagon infusion, with urea accounting for the increased excretion. Excretion of 3-methylhistidine was unchanged. Plasma amino acid concentration was strikingly reduced on the first day of glucagon infusion, where it stabilized. Forearm flux showed a slight net release of amino acid nitrogen during glucose infusion. Addition of glucagon to the glucose infusion resulted in a net uptake of nitrogen by forearm skeletal muscle. These evidences strongly suggest that glucagon infusion in normal man increases ureagenesis, not only at the expense of the free amino acid pool, but by the hydrolysis of visceral protein as well, with muscle protein being maintained.