title: Impaired expression and function of breast cancer resistance protein (Bcrp) in brain cortex of streptozocin-induced diabetic rats.
abstract: The aim of this study was to investigate whether diabetes mellitus (DM) affected breast cancer resistance protein (Bcrp) function and expression in rat brain. 5-week and 8-week diabetic rats were induced by streptozocin (STZ). Bcrp expression and function in brain cortex were assessed by western blot and measuring the brain-to-plasma concentration ratios of two typical substrates prazosin and cimetidine, respectively. The diabetic rats were treated with three different agents insulin, aminoguanidine (AG) and metformin (MET). It was found that the brain-to-plasma ratios of prazosin and cimetidine in diabetic rats were significantly higher than those of control rats, which were dependent on duration of diabetes. Lower levels of Bcrp were found in brain cortex of diabetic rats, which were in parallel with increase of brain-to-plasma ratios. Insulin treatment may attenuate the impairment of Bcrp expression and function induced by diabetes. Aminoguanidine and metformin treatment did not prevent the impairment of Bcrp function and expression in brain cortex of diabetic rats. All results gave a conclusion that STZ-induced DM may induce the impairment of function and expression of Bcrp in brain cortex, and lower levels of insulin may mainly contribute to Bcrp dysfunction in brain.
authors.affiliation: Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Tongjiaxiang No. 24, Nanjing 210009, China.
authors.forename: Yu-Chun
authors.initials: YC
authors.lastname: Liu
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Liu
authors.forename: Hui-Wen
authors.initials: HW
authors.lastname: Yang
authors.forename: Tao
authors.initials: T
authors.lastname: Wen
authors.forename: Yang
authors.initials: Y
authors.lastname: Shang
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Liu
authors.forename: Lin
authors.initials: L
authors.lastname: Xie
authors.forename: Guang-Ji
authors.initials: GJ
authors.lastname: Wang
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D002927:Cimetidine / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D008297:Male; D011224:Prazosin / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin / Q000494:pharmacology*
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; C489249:Abcg2 protein, rat; D013311:Streptozocin; D002927:Cimetidine; D011224:Prazosin