Enhancement of bile acid-induced biliary lipid secretion by streptozotocin in rats: role of insulin deficiency

Abstract

Diabetes is thought to be associated with alterations in biliary function involved in a higher prevalence of gallstones in diabetic patients. However, the presence of supersaturated bile in diabetes is still controversial. To gain information on this point, we studied the effect of insulin deficiency on biliary secretion of bile acid, phospholipid, and cholesterol in anesthetized rats. Diabetes was induced by streptozotocin injection (6 mg/100 gm body weight, intraperitoneally). Experiments were carried out at different times (from 1 to 28 days) after diabetes induction. Some rats received insulin (10.5 U/100 gm body weight; divided into five doses) from the third to the sixth day after administration of streptozotocin. Shortly after streptozotocin injection (1 day), bile acid output was decreased but later markedly increased (from 6 days). However, cholestasis was apparent in all insulin-deficient groups. Biliary lecithin concentrations and secretion rate were enhanced from the first day of diabetes. Moreover, an increase in the biliary percentage of lecithin (from 53% to 71% of total biliary phospholipid), which was counterbalanced mainly by a decrease in the biliary concentration of phosphatidylethanolamine, was observed in rats with diabetes for 6 days. Cholesterol concentrations in bile were also higher in diabetic rats. However, the lithogenic index (i.e., percent of cholesterol saturation) was never higher than in healthy rats (55.7%). Cholesterol output induced by taurocholate infusion was not significantly different in control and in 6-days diabetic rats. Nevertheless, biliary lecithin secretion stimulated by taurocholate infusion was markedly increased (the number of lecithin molecules accompanying every 100 molecules of bile acid into bile was 7 and 18 in control and diabetic rats, respectively, at bile acid rates lower than 150 nmol/min per gram liver). Administration of insulin to diabetic rats reversed the above-reported changes. These results indicate that streptozotocin induces profound changes in the mechanisms responsible for bile acid-induced biliary lipid secretion, which are due to the insulin deficiency rather than to a direct hepatotoxic effect of the diabetogenic drug.