Differential effects of streptozotocin-induced diabetes on expression of hepatic ABC-transporters in rats

Background & Aims: Diabetes mellitus Is associated with changes In bile formation. The aim of our study was to investigate the molecular basis for these changes In rats with experimentally Induced diabetes. Methods: Expression of bile canalicular transporters was studied by reverse-transcription polymerase chain reaction, Immunoblotting, and immunohistochemistry In control, streptozotocin-diabetic, and insulin-treated diabetic rats. Bile formation was studied under basal conditions and during stepwise Increasing Intravenous Infusion of taurocholate to determine bile salt secretory rate maximum (SRm). Results: In diabetic rats, hepatic gene and protein expression of the multidrug resistance P-glycoprotein type 2 (Mdr2) were Increased by 105% and 530%, respectively, associated with Increased biliary phospholipid output (+520%) and phosphollpid/bile salt ratio (+77%). Protein levels of the canalicular bile salt export pump (Bsep) were unchanged In diabetic rats, but basal biliary bile salt output and the SRm of taurocholate were Increased by 260% and 130%, respectively, compared with controls. Alterations In transporter expression and bile formation were partly reversed by Insulin administration. The bile salt SRm was strongly correlated with biliary phospholipid concentration (P <0.001, R = 0.82). Conclusions: Induction of Mdr2 expression and biliary, phospholipid secretion, rather than Bsep expression, appears to be responsible for the enhanced capacity of biliary bile salt secretion In experimentally induced diabetes.