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 phospholipid/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.
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 diabeticrats. 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 diabeticrats, 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 phospholipid/bile salt ratio (+77%). Protein levels of the canalicular bile salt export pump (Bsep) were unchanged in diabeticrats, 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.
Authors: Jan Freark de Boer; Wijtske Annema; Marijke Schreurs; Jelske N van der Veen; Markus van der Giet; Niels Nijstad; Folkert Kuipers; Uwe J F Tietge Journal: J Lipid Res Date: 2011-12-18 Impact factor: 5.922
Authors: Tineke Kok; Vincent W Bloks; Henk Wolters; Rick Havinga; Peter L M Jansen; Bart Staels; Folkert Kuipers Journal: Biochem J Date: 2003-02-01 Impact factor: 3.857
Authors: Fadi Annaba; Ke Ma; Pradeep Kumar; Amish K Dudeja; Rhonda D Kineman; Benjamin L Shneider; Seema Saksena; Ravinder K Gill; Waddah A Alrefai Journal: Am J Physiol Gastrointest Liver Physiol Date: 2010-07-22 Impact factor: 4.052
Authors: V W Bloks; W M Bakker-Van Waarde; H J Verkade; I P Kema; H Wolters; E Vink; A K Groen; F Kuipers Journal: Diabetologia Date: 2003-11-14 Impact factor: 10.122