Villanueva G R, Herreros M, Perez-Barriocanal F, Bolaños J P, Bravo P, Marin J J
Department of Physiology, University of Salamanca, Spain.
J Lab Clin Med. 1990 Apr;115(4):441-8.
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.
糖尿病被认为与胆汁功能改变有关，而这涉及糖尿病患者胆结石患病率较高。然而，糖尿病患者胆汁过饱和的情况仍存在争议。为了获取这方面的信息，我们研究了胰岛素缺乏对麻醉大鼠胆汁酸、磷脂和胆固醇胆汁分泌的影响。通过腹腔注射链脲佐菌素（6毫克/100克体重）诱导糖尿病。在糖尿病诱导后的不同时间（1至28天）进行实验。一些大鼠在注射链脲佐菌素后的第三天至第六天接受胰岛素（10.5单位/100克体重；分为五剂）。链脲佐菌素注射后不久（1天），胆汁酸输出减少，但随后显著增加（从6天开始）。然而，所有胰岛素缺乏组均出现明显的胆汁淤积。糖尿病第一天起，胆汁卵磷脂浓度和分泌率就升高。此外，糖尿病6天的大鼠中观察到胆汁卵磷脂百分比增加（从总胆汁磷脂的53%增至71%），这主要由磷脂酰乙醇胺胆汁浓度降低所抵消。糖尿病大鼠胆汁中的胆固醇浓度也较高。然而，成石指数（即胆固醇饱和度百分比）从未高于健康大鼠（55.7%）。对照组和糖尿病6天大鼠中，牛磺胆酸盐输注诱导的胆固醇输出无显著差异。然而，牛磺胆酸盐输注刺激的胆汁卵磷脂分泌显著增加（在肝胆汁酸速率低于150纳摩尔/分钟每克时，对照组和糖尿病大鼠中每100分子胆汁酸进入胆汁时伴随的卵磷脂分子数分别为7和18）。给糖尿病大鼠注射胰岛素可逆转上述变化。这些结果表明，链脲佐菌素诱导了负责胆汁酸诱导胆汁脂质分泌的机制发生深刻变化，这是由于胰岛素缺乏而非致糖尿病药物的直接肝毒性作用。
