Document Detail


Pregnancy represses induction of efflux transporters in livers of type I diabetic mice.
MedLine Citation:
PMID:  23319174     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: 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:
Lauren M Aleksunes; Jialin Xu; Eugenia Lin; Xia Wen; Michael J Goedken; Angela L Slitt
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-01-15
Journal Detail:
Title:  Pharmaceutical research     Volume:  30     ISSN:  1573-904X     ISO Abbreviation:  Pharm. Res.     Publication Date:  2013 Sep 
Date Detail:
Created Date:  2013-08-21     Completed Date:  2014-03-18     Revised Date:  2014-09-02    
Medline Journal Info:
Nlm Unique ID:  8406521     Medline TA:  Pharm Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2209-20     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
ATP-Binding Cassette Transporters / genetics*
Animals
Diabetes Mellitus, Experimental / genetics*,  metabolism
Diabetes Mellitus, Type 1 / genetics*,  metabolism
Down-Regulation
Female
Liver / metabolism*
Male
Mice
Mice, Inbred C57BL
NF-E2-Related Factor 2 / metabolism
PPAR gamma / metabolism
Pregnancy
Pregnancy in Diabetics / genetics*,  metabolism
RNA, Messenger / genetics
Receptors, Cytoplasmic and Nuclear / metabolism
Signal Transduction
Up-Regulation
Grant Support
ID/Acronym/Agency:
DK080774/DK/NIDDK NIH HHS; ES005022/ES/NIEHS NIH HHS; ES016042/ES/NIEHS NIH HHS; ES020522/ES/NIEHS NIH HHS; P30 ES005022/ES/NIEHS NIH HHS; R00 DK080774/DK/NIDDK NIH HHS; R01 ES016042/ES/NIEHS NIH HHS; R01 ES020522/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/NF-E2-Related Factor 2; 0/Nfe2l2 protein, mouse; 0/PPAR gamma; 0/RNA, Messenger; 0/Receptors, Cytoplasmic and Nuclear; 0/farnesoid X-activated receptor
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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