title: Tissue-specific alterations in expression and function of P-glycoprotein in streptozotocin-induced diabetic rats.
abstract: OBJECTIVE
  To investigate the changes of expression and function of P-glycoprotein (P-GP) in cerebral cortex, hippocampus, liver, intestinal mucosa and kidney of streptozocin-induced diabetic rats.
  
  
  METHODS
  Diabetic rats were prepared via a single dose of streptozocin (65 mg/kg, ip). Abcb1/P-GP mRNA and protein expression levels in tissues were evaluated using quantitative real time polymerase chain reaction (QRT-PCR) analysis and Western blot, respectively. P-GP function was investigated via measuring tissue-to-plasma concentration ratios and body fluid excretion percentages of rhodamine 123.
  
  
  RESULTS
  In 5- and 8-week diabetic rats, Abcb1a mRNA levels were significantly decreased in cerebral cortices and intestinal mucosa, but dramatically increased in hippocampus and kidney. In liver, the level was increased in 5-week diabetic rats, and decreased in 8-week diabetic rats. Abcb1b mRNA levels were increased in cerebral cortex, hippocampus and kidney, but reduced in liver and intestinal mucosa in the diabetic rats. Western blot results were in accordance with the alterations of Abcb1a mRNA levels in most tissues examined. P-GP activity was markedly decreased in most tissues of diabetic rats, except kidney tissues.
  
  
  CONCLUSIONS
  Alterations in the expression and function of Abcb1/P-GP under diabetic conditions are tissue specific, Abcb1 specific and diabetic duration-dependent.
authors.affiliation: Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Lu-lu
authors.initials: LL
authors.lastname: Zhang
authors.forename: Liang
authors.initials: L
authors.lastname: Lu
authors.forename: Shi
authors.initials: S
authors.lastname: Jin
authors.forename: Xin-yue
authors.initials: XY
authors.lastname: Jing
authors.forename: Dan
authors.initials: D
authors.lastname: Yao
authors.forename: Nan
authors.initials: N
authors.lastname: Hu
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Ru
authors.initials: R
authors.lastname: Duan
authors.forename: Xiao-dong
authors.initials: XD
authors.lastname: Liu
authors.forename: Guang-ji
authors.initials: GJ
authors.lastname: Wang
authors.forename: Lin
authors.initials: L
authors.lastname: Xie
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D006624:Hippocampus / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D012333:RNA, Messenger