Opposite regulation of hepatic breast cancer resistance protein in type 1 and 2 diabetes mellitus
He, Lei1,2; Yang, Yuan3; Guo, Cen1,2; Yao, Dan2; Liu, Hui-hui2; Sheng, Jing-jing2; Zhou, Wei-ping3; Ren, Jin2; Liu, Xiao-dong1; Pan, Guo-yu2
刊名EUROPEAN JOURNAL OF PHARMACOLOGY
2014-02-05
卷号724页码:185-192
关键词Diabetes Sandwich cultured rat hepatocytes Breast cancer resistant protein
ISSN号0014-2999
DOI10.1016/j.ejphar.2013.12.008
文献子类Article
英文摘要Previous studies on diabetes have reported controversial results with regard to transporters in liver. The present study aimed to explore changes in hepatic breast cancer resistance protein (BCRP) expression and functions, as well as the possible underlying mechanisms, in type 2 diabetic patients, type 1 (streptozotocin-induced), and type 2 (Goto Kakizaki) diabetic rats. Protein and mRNA levels of human (h) and rat (r) BCRP were investigated using Western blot and quantitative polymerase chain reaction analyses. Functions of liver rBCRP were evaluated using rosuvastatin. Sandwich cultured rat hepatocytes (SCRH) were cultured with D-glucose, insulin, or oleic acid for 72 h, and rBCRP mRNA was detected. The effect of oleic acid on rBCRP function in SCRH was also investigated using rosuvastatin. Results showed that liver rBCRP mRNA levels decreased to 20% in type 1 diabetic rats, whereas that in diabetic patients and GK rats significantly increased threefold and twentyfold, respectively. No changes were observed in h/rBCRP protein levels of type 2 diabetic patients and GK rats. The functions of rBCRP significantly declined in type 1 diabetic rats but showed no significant. changes in GK rats. The data from SCRH indicated that D-glucose decreased rBCRP mRNA level to 60%. Oleic acid increased rBCRP mRNA in SCRH by approximately eightfold but decreased rBCRP function to 50%. Therefore, h/rBCRP expression and Functions were oppositely regulated in type 1 and type 2 diabetes mellitus subjects. Alternations in D-glucose, insulin, and free fatty acid levels in plasma might contribute to the changes in h/rBCRP expression and functions. (C) 2013 Elsevier B.V. All rights reserved
资助项目National Science Foundation of China[81302836] ; Major National Science and Technology Programs[2012ZX09301001-006] ; Major National Science and Technology Programs[2012ZX09302003] ; National High Technology Research and Development Program of China[2013AA032202]
WOS关键词DRUG-DRUG INTERACTIONS ; P-GLYCOPROTEIN ; BILIARY-EXCRETION ; RAT HEPATOCYTES ; IN-VIVO ; STREPTOZOTOCIN ; TRANSPORTER ; EXPRESSION ; CELLS ; MICE
WOS研究方向Pharmacology & Pharmacy
语种英语
出版者ELSEVIER SCIENCE BV
WOS记录号WOS:000331140500023
内容类型期刊论文
源URL[http://119.78.100.183/handle/2S10ELR8/277190]  
专题药物安全性评价中心
通讯作者Liu, Xiao-dong
作者单位1.China Pharmaceut Univ, Key Lab Drug Metab & Pharmacokinet, Nanjing 210009, Jiangsu, Peoples R China;
2.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Safety Evaluat & Res, Shanghai 201203, Peoples R China;
3.Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Shanghai 200438, Peoples R China
推荐引用方式
GB/T 7714
He, Lei,Yang, Yuan,Guo, Cen,et al. Opposite regulation of hepatic breast cancer resistance protein in type 1 and 2 diabetes mellitus[J]. EUROPEAN JOURNAL OF PHARMACOLOGY,2014,724:185-192.
APA He, Lei.,Yang, Yuan.,Guo, Cen.,Yao, Dan.,Liu, Hui-hui.,...&Pan, Guo-yu.(2014).Opposite regulation of hepatic breast cancer resistance protein in type 1 and 2 diabetes mellitus.EUROPEAN JOURNAL OF PHARMACOLOGY,724,185-192.
MLA He, Lei,et al."Opposite regulation of hepatic breast cancer resistance protein in type 1 and 2 diabetes mellitus".EUROPEAN JOURNAL OF PHARMACOLOGY 724(2014):185-192.
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