Effects of glucagon on urinary excretion of urea and on plasma ammonia level in argininosuccinate synthetase deficiency

Glucagon, a potent inducer of urea cycle enzymes, was administered subcutaneously, at a dose of 0.5 mg once a day, for 7 days to two citrullinemic patients. During this period, plasma NH3 levels in case 1 decreased significantly (P < 0.05 compared to levels before administration) and daily urinary excretion of urea N increased significantly (P < 0.05). For 1 week after the cessation of administration, the daily urinary excretion of urea N was significantly higher than the level before administration (P < 0.05), the plasma citrulline level during glucagon administration was lower than that before administration. In case 2, glucagon administration also decreased the plasma NH3 level (although the decrease was not statistically significant), and significantly increased daily urinary excretion of urea N (P < 0.05 compared to levels before administration). For 1 week after the cessation of glucagon administration the plasma citrulline level was significantly lower than that before administration (P < 0.05). These results indicate that glucagon significantly increases the urinary excretion of urea in the late onset form of argininosuccinate synthetase deficiency and that it may also decrease plasma NH3 levels in some patients with the deficiency.