Role of glucagon in cholecystokinin-stimulated bile flow in dogs.

Abstract

Although many choleretic agents are known, their physiological roles and interrelationships in increasing bile flow remain largely undetermined. Exogenous cholecystokinin (CCK), glucagon, and insulin are stimulants of hepatic bile flow in animals and humans. Of possible importance in the choleresis produced by CCK is the stimulation by exogenous CCK of glucagon and insulin release from the pancreas. This research evaluates the role of glucagon and insulin in the choleresis produced by CCK. Dogs with chronic biliary and gastric fistulas were used. The synthetic octapeptide of CCK (CCK-8) administered in increasing doses produced progressive increases in bile volume, bile bicarbonate secretion, and bile chloride concentration and output. The choleresis produced by CCK-8 was qualitatively similar to that produced by intravenous glucagon. CCK-8 administration in increasing doses produced progressive increases in plasma glucagon. When bile flow changes during CCK-8 administration were correlated with changes in plasma glucagon, significant correlation existed. CCK-8 significantly increased serum insulin concentration only at the highest dose of CCK-8 administered. Somatostatin is an inhibitor of hormone release. Administration of somatostatin, along with CCK-8, inhibited the choleresis and the increased plasma glucagon produced by CCK-8 administration alone. During acute experiments in anesthetized dogs, the pancreas and stomach were removed to eliminate endogenous glucagon and insulin release. (ABSTRACT TRUNCATED AT 250 WORDS)