Insulin-induced choleresis in relation to insulin concentrations in plasma and bile in the cat

In experiments on fasting, chloralose-anesthetized cats the concentrations of insulin and glucagon in arterial or portal plasma and bile were studied during insulin-induced choleresis. The administration of insulin in single doses (0.1-1.0 U x kg-1) and infusions (0.001-0.01 U x kg-1 x min-1) resulted in parallel increases in bile flow and 14C-erythritol clearances of 17%-96%, whereas the net ductular fluid transport and the biliary excretion rate of bile acids remained unchanged. Insulin therefore stimulated the bile acid-independent fraction of the canalicular bile formation. When corrected for the hepatic transit time of insulin (25 min) the initial phase of insulin choleresis was closely related in time to the plasma (30-5000 microunits x ml-1) and biliary (40-210 microunits x ml-1) concentrations of insulin. Bile flow was stimulated even at plasma insulin concentrations similar to those seen postprandially. It is concluded that insulin-induced choleresis to a great extent can be explained by direct, hepatic actions of the hormone, but a delayed release of glucagon may be of importance for the terminal phase of insulin choleresis. The results also demonstrate that insulin crosses the liver by an intercellular pathway. This mode of transport could be of importance for its action on bile production.