Hepatic transport of bilirubin in rats with streptozotocin-induced diabetes.
This study was undertaken to evaluate the effects of streptozotocin-induced diabetes on the hepatic transport of bilirubin in male Wistar rats. Rats were pretreated with streptozotocin (60 mg/kg i.p.) to induce uncontrolled diabetes. Six days later endogenous biliary excretion and plasma bilirubin concentration were significantly enhanced compared to control animals (+36% and +46%, respectively), while the blood levels of free hemoglobin remained unchanged. Following a bilirubin load, the maximal biliary excretion of the pigment (Tm) in diabetic animals was significantly enhanced compared to control animals (+49%). Liver and plasma bilirubin concentrations at the end of bilirubin administration were significantly reduced (-28% and -30%, respectively). Bilirubin UDP-glucuronosyltransferase activity and UDP-glucose concentration in liver were significantly enhanced (+31% and +81%, respectively), as was the biliary excretion of unconjugated bilirubin (+37%) and bilirubin mono- (+38%) and diconjugates (+53%). When streptozotocin-diabetic rats were treated with insulin, the parameters of bilirubin transport and metabolism were significantly reduced compared to diabetic animals receiving no hormone replacement. In summary, our data indicate that in short-term streptozotocin-diabetic rats there is increased bilirubin production as well as enhanced hepatic conjugation and subsequent biliary excretion of the pigment. These effects appear to be a direct consequence of diabetes.