Impaired expression and function of breast cancer resistance protein (Bcrp) in brain cortex of streptozocin-induced diabetic rats.
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.
Liu
Yu-Chun
YC
Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Tongjiaxiang No. 24, Nanjing 210009, China.
Liu
Hai-Yan
HY
Yang
Hui-Wen
HW
Wen
Tao
T
Shang
Yang
Y
Liu
Xiao-Dong
XD
Xie
Lin
L
Wang
Guang-Ji
GJ
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*
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; C489249:Abcg2 protein, rat; D013311:Streptozocin; D002927:Cimetidine; D011224:Prazosin