The direct effect of insulin on canalicular bile flow

Previous experimental studies in dogs have demonstrated the choleretic effects of insulin administered in physiologic doses. In our experiment the isolated perfused rat liver was used as an in situ model for demonstrating the direct effects of insulin on bile salt independent canalicular bile flow. Livers were initially perfused with oxygenated Krebs-Ringer buffer solution of 20% hematocrit after which sodium taurocholate (18.3 mg hr-1) was infused to stabilize bile flow. Insulin (0.5 unit kg-1 hr-1) or saline was then given for a 90-min test period. Control (C) and experimental (E) rats were perfused simulataneously (n = 11). Bile flow was significantly greater in the experimental (21.76 +/- 2.16 microliters g liver-1 15 min-1) than the control (16.87 +/- 2.08 microliters g liver-1 15 min-1) group (P less than .01). In addition, the percentage change in flow in individual rats from baseline values was significantly different with peak effect occurring 45 min after start of hormone infusion (E = +19 +/- 3%, C = -5 +/- 7%) (P less than 0.003). Bile analysis revealed stable bile salt concentrations (E = 7.41 +/- .25, C = 7.8 +/- .24 mM ml-1) and stable bile salt outputs (E = 1.68 +/- .14, C = 1.33 +/- .13 mM 15 min-1) for both groups. Biliary cholesterol outputs did not differ between groups (E = 42.6 +/- 4.8, C = 38.2 +/- 7.4 micrograms 15 min-1), nor did phospholipid outputs (E = 3.56 +/- .63, C = 2.71 +/- .57 mg 15 min-1). These data support the hypothesis that the choleretic action of insulin is a direct one on the hepatocyte, requiring no intermediate step or mediator.