Effect of verapamil on insulin-stimulated choleresis

Insulin is one of several neurohumoral substances known to have a choleretic effect in vivo and in the isolated perfused rat liver. Infusion of insulin in the perfused rat liver preparation results in stimulation of bile acid-independent bile flow evidenced by increased bile flow, decreased bile acid concentration, and stable bile acid output. The mechanism of insulin-stimulated choleresis is unknown but may involve calcium as an intracellular second messenger. The present studies were performed to assess the role of membrane calcium channels in mediating choleresis and insulin-stimulated bile acid-independent bile flow in the in situ perfused rat liver. We have shown that verapamil, a specific calcium channel blocker, has no effect on bile flow, bile acid concentration, or bile acid output during bile acid-stimulated choleresis at a taurocholate infusion rate of 40 or 80 nmole/g liver/min. Insulin caused a significant increase in bile flow (18-30%) and a decrease in bile acid concentration (13-21%) without affecting bile acid output at a taurocholate infusion rate of 40 or 80 nmole/g liver/min. Verapamil failed to inhibit insulin-stimulated choleresis at a taurocholate infusion rate of 80 nmole/g liver/min. Although we observed an insulin-stimulated increase in bile flow and a decrease in bile acid concentration in the presence of verapamil at a taurocholate infusion rate of 40 nmole/g liver/min, these changes failed to reach statistical significance. We conclude that verapamil has no effect on choleresis or insulin-stimulated bile flow in the perfused rat liver and that the mechanism by which insulin promotes bile acid-independent bile flow is not mediated by verapamil-sensitive calcium channels.