Tissue-specific damage in expression and function of breast cancer resistance protein in streptozotocin-induced diabetic rats

The purpose of the study was to investigate whether diabetes mellitus would alter breast cancer resistance protein (BCRP) expression and function in the cerebral cortex,hippocampus,liver,intestinal mucosa and kidney of rat and whether insulin treatment would reverse the alteration caused by diabetes.Abnormal factors in diabetic blood serum altering the expression and function of BCRP were investigated using Caco-2 and HepG-2 cells.Diabetic rats were induced by an intraperitoneal administration of 55 mg/kg of streptozotocin.ATP-binding cassette transporter G2(ABCG2)/BCRP mRNA and protein expression levels in the indicated tissues were evaluated by quantitative real time polymerase chain reaction (QT-PCR) analysis and Western blot,respectively.BCRP functional activities were estimated by the uptake of prazosin in Caco-2 and HepG-2 cells.QT-PCR analysis revealed that ABCG2 mRNA levels were significantly decreased in cerebral cortex,liver and intestinal mucosa,but were dramatically increased in hippocampus and kidney of 5- and 8-week diabetic rats.Western blot results were in accordance with the alterations of ABCG2 mRNA levels in most tissues.Uptake assay results demonstrated that high insulin and high glucose may cause the down-regulation of BCRP in Caco-2 and HepG-2 cells.The results demonstrated that diabetes damaged the ABCG2/BCRP expression and function in a tissue-specific manner;and in rat liver and intestinal mucosa,the alteration of BCRP under diabetic condition may be caused by high glucose level.