Interaction of Insulin, Glucagon, and DBcAMP on Bile Acid-Independent Bile Production in the Rat

Abstract

In experiments on fasted, pentobarbital-anesthetized rats the effect of insulin (1 U X kg-1, followed by 0.05 U X kg-1 X min-1), glucagon (0.5 micrograms X kg-1 X min-1), and dibutyrylic cyclic AMP (DBcAMP) (0.5 mumol X kg-1 X min-1) on bile flow and composit8ion was examined. Infusion of these substances resulted in maximal increases only in the bile acid-independent bile formation, and insulin appeared to be a more powerful stimulant of bile production than glucagon or DBcAMP. When bile production was first stimulated maximally with glucagon or DBcAMP, supplementary infusion of insulin increased bile production significantly. When administration of glucagon or DBcAMP supplemented maximal infusion of insulin, only DBcAMP resulted in a further increase in bile production. Bile production was, however, increased by supplementary glucagon infusion, when a submaximal dosage of insulin was given. No additive effect of glucagon and DBcAMP on bile secretion was observed. The results suggest that glucagon induces choleresis in rats via liberation of cAMP and that the mechanisms of glucagon choleresis differ at least partly from those involved in insulin choleresis. The results are compatible with an insulin-produced inhibition of the adenylate cyclase and activation of the phosphodiesterase in the liver. In accordance with present knowledge of the biological effects of insulin and glucagon the choleretic response to both hormones may be secondary to stimulation of Na-K-ATPase located to the hepatocellular membrane.