UNRESPONSIVENESS OF HEPATIC NITROGEN-METABOLISM TO GLUCAGON-INFUSION IN PATIENTS WITH CIRRHOSIS - DEPENDENCE ON LIVER-CELL FAILURE

Glucagon exerts an up-regulatory effect on hepatic nitrogen metabolism in healthy subjects, but its potential role in the presence of liver failure is uncertain. The effects of glucagon on urea synthesis and he patic nitrogen clearance during alanine infusion were studied in five control subjects and six cirrhotic patients in paired experiments at s pontaneous glucagon concentrations and at high physiological glucagon levels (almost-equal-to 300 to 500 pmol . L-1) induced by a 7.5-hr con tinuous glucagon infusion. In all experiments the urea nitrogen synthe sis rate increased linearly with increasing alpha-amino-nitrogen conce ntrations. At spontaneous glucagon concentrations the dynamics of alph a-amino nitrogen to urea nitrogen conversion (functional hepatic nitro gen clearance) were significantly reduced in cirrhosis (23.2 +/- 6.7 L . hr-1 vs. 35.3 +/- 8.0 L . hr-1, p < 0.05) in relation to decreased liver function. Glucagon superinfusion caused a 63% increase in the dy namics of the process in controls (57.7 +/- 11.0 L . hr-1; p vs. spont aneous glucagon, p < 0.01), whereas in cirrhosis it increased on avera ge by only 15% (26.7 +/- 10.7; p = NS). The glucagon-induced change in functional hepatic nitrogen clearance significantly correlated with g alactose elimination capacity and antipyrine clearance (r = 0.905 and 0.964, respectively). Glucagon, in high physiological concentrations a chieved with glucagon infusion, does not produce significant effects o n hepatic nitrogen metabolism in cirrhosis. The reduced sensitivity of the cirrhotic liver to glucagon seems to be dependent on decreased he patocellular function. These data do not support the role of glucagon as a ''catabolic'' hormone in cirrhosis.