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  • Title: Down-regulation of hepatic and intestinal Abcg5 and Abcg8 expression associated with altered sterol fluxes in rats with streptozotocin-induced diabetes.
    Author: Bloks VW, Bakker-Van Waarde WM, Verkade HJ, Kema IP, Wolters H, Vink E, Groen AK, Kuipers F.
    Journal: Diabetologia; 2004 Jan; 47(1):104-12. PubMed ID: 14618236.
    Abstract:
    AIM/HYPOTHESIS: Type I diabetes is associated with altered hepatic bile formation and increased intestinal cholesterol absorption. The aim of this study was to evaluate whether altered expression of the ATP-Binding Cassette half-transporters Abcg5 and Abcg8, recently implicated in control of both hepatobiliary cholesterol secretion and intestinal cholesterol absorption, contributes to changed cholesterol metabolism in experimental diabetes. METHODS: mRNA and protein expression of Abcg5 and Abcg8 were determined in the liver and intestine of rats with streptozotozin-induced diabetes and related to relevant metabolic parameters in plasma, liver and bile. RESULTS: Hepatic mRNA expression of both Abcg5 (-76%) and Abcg8 (-71%) was reduced in diabetic rats when compared to control rats. In spite of increased HDL cholesterol, considered a major source of biliary cholesterol, secretion of the sterol into bile relative to that of bile salts was reduced by 65% in diabetic animals. Intestinal mRNA expression of Abcg5 (-47%) and Abcg8 (-43%) as well as Abcg5 protein contents were also reduced in insulin-deficient animals. This was accompanied by a three- to four-fold increase in plasma beta-sitosterol and campesterol concentrations and by a doubling of the calculated apparent cholesterol absorption. These effects partially normalized upon insulin supplementation. CONCLUSION/INTERPRETATION: Our data indicate that effects of insulin-deficiency on bile composition and cholesterol absorption in rats are, at least partly, attributable to changes in hepatic and intestinal Abcg5 and Abcg8 expression.
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