Hyperglucagonemia in cirrhosis: altered secretion and sensitivity to glucagon.

Plasma glucagon concentration was elevated 2- to 6-fold in cirrhotic patients with spontaneous portal systemic shunting or surgically induced portacaval anastomosis but was comparable to controls in cirrhotics without portal-systemic shunting. The metabolic clearance rate of glucagon (mol wt 3500) was normal in all of the cirrhotic groups, but the estimated basal systemic delivery rate of glucagon was increased 2- to 6-fold in the hyperglucagonemic patients. The blood glucose response to infusion of glucagon (3 ng per kg per min) was reduced in the cirrhotics with portal-systemic shunting or portacaval anastomosis, and correlated inversely with the delivery rate of endogenous glucagon. Administration of ammonium chloride (3 g) failed to elevate plasma glucagon concentration. It is concluded that hyperglucagonemia in cirrhosis is a consequence of hypersecretion rather than decreased hormonal catabolism. A negative feedback signal may exist between hepatic sensitivity to glucagon and the secretion of this hormone.