Glucagon increases hepatic efficacy for urea synthesis.

The effect of glucagon on the relation between urea synthesis and blood amino acid concentration was studied in seven healthy volunteers. Alanine was given as prime-continuous infusions and, after 1 hr for equilibration, the urea nitrogen synthesis rate was measured in two periods of about 2 hrs as urinary excretion corrected for accumulation and intestinal hydrolysis. During one of the periods, glucagon was infused to obtain a constant concentration of 200-1200 ng/l. The spontaneous urea synthesis during the alanine infusion was 86-141 mmol/hr and linearly related to the alanine concentrations of 1.33-2.99 mmol/l. The hepatic clearance of alanine-nitrogen to urea-nitrogen, assessed by the ratio between the increase in the urea synthesis rate and alanine concentration, was 23 +/- 4 l/hr (mean +/- S.D.). Glucagon increased the rate of urea synthesis by 35 +/- 11 mmol/hr (p less than 0.02) and decreased the alanine concentration by 0.22 +/- 0.06 mmol/l (p less than 0.01). Glucagon increased the hepatic nitrogen clearance to an average of 42 +/- 13 l/hr (p less than 0.01). The difference between infusion of amino-nitrogen and appearance of urea-nitrogen was +15 +/- 10 mmol/hr during alanine infusion alone and -11 +/- 25 mmol/hr during exogenous glucagon. The loss of nitrogen could be accounted for by depletion of non-alanine amino acids from the blood. Glucagon increases the efficacy of urea synthesis, which may be of importance for catabolism by changing the hepatic contribution to nitrogen homeostasis.