title: Pregnancy represses induction of efflux transporters in livers of type I diabetic mice.
abstract: OBJECTIVE
  To determine whether down-regulation of transcription factor signaling during pregnancy disrupts the induction of efflux transporters in type I diabetic mice.
  
  
  METHODS
  Type I diabetes was induced in female C57BL/6 mice with multiple low dose intraperitoneal injections of streptozotocin (STZ) at least 2 weeks prior to mating with normoglycemic male mice. On gestation day 14, livers were collected from vehicle- and STZ-treated non-pregnant and pregnant mice for quantification of efflux transporter and transcription factor signaling.
  
  
  RESULTS
  STZ treatment up-regulated expression of Mrp1-5, Mdr1, Abcg5, Abcg8, Bcrp, and Bsep mRNA and/or protein in the livers of non-pregnant mice. Interestingly, little to no change in transporter expression was observed in STZ-treated pregnant mice compared to vehicle- and STZ-treated non-pregnant mice.
  
  
  CONCLUSIONS
  This study demonstrates the opposing regulation of hepatobiliary efflux transporters in response to diabetes and pregnancy and points to PPARγ, Nrf2, and FXR as candidate pathways underlying the differential expression of transporters.
authors: Department of Pharmacology and Toxicology, Rutgers University Ernest Mario School of Pharmacy, Piscataway, New Jersey, USA. aleksunes@eohsi.rutgers.edu
authors: Lauren M
authors: LM
authors: Aleksunes
authors: Jialin
authors: J
authors: Xu
authors: Eugenia
authors: E
authors: Lin
authors: Xia
authors: X
authors: Wen
authors: Michael J
authors: MJ
authors: Goedken
authors: Angela L
authors: AL
authors: Slitt
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D018528:ATP-Binding Cassette Transporters; D051267:NF-E2-Related Factor 2; D047495:PPAR gamma; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated; C495636:Nfe2l2 protein, mouse