Show simple item record

dc.contributor.authorKilic, Gamze
dc.contributor.authorAlvarez-Mercado, Ana I.
dc.contributor.authorZarrouki, Bader
dc.contributor.authorOpland, Darren
dc.contributor.authorLiew, Chong Wee
dc.contributor.authorAlonso, Laura C.
dc.contributor.authorMyers Jr, Martin G.
dc.contributor.authorJonas, Jean-Christophe
dc.contributor.authorPoitout, Vincent
dc.contributor.authorKulkarni, Rohit N.
dc.contributor.authorMauvais-Jarvis, Franck
dc.date2022-08-11T08:08:30.000
dc.date.accessioned2022-08-23T15:57:25Z
dc.date.available2022-08-23T15:57:25Z
dc.date.issued2014-02-03
dc.date.submitted2014-10-20
dc.identifier.citationPLoS One. 2014 Feb 3;9(2):e87941. doi: 10.1371/journal.pone.0087941. eCollection 2014. <a href="http://dx.doi.org/10.1371/journal.pone.0087941">Link to article on publisher's site</a>
dc.identifier.issn1932-6203 (Linking)
dc.identifier.doi10.1371/journal.pone.0087941
dc.identifier.pmid24498408
dc.identifier.urihttp://hdl.handle.net/20.500.14038/30192
dc.description.abstractThe female steroid, 17beta-estradiol (E2), is important for pancreatic beta-cell function and acts via at least three estrogen receptors (ER), ERalpha, ERbeta, and the G-protein coupled ER (GPER). Using a pancreas-specific ERalpha knockout mouse generated using the Cre-lox-P system and a Pdx1-Cre transgenic line (PERalphaKO (-)/(-)), we previously reported that islet ERalpha suppresses islet glucolipotoxicity and prevents beta-cell dysfunction induced by high fat feeding. We also showed that E2 acts via ERalpha to prevent beta-cell apoptosis in vivo. However, the contribution of the islet ERalpha to beta-cell survival in vivo, without the contribution of ERalpha in other tissues is still unclear. Using the PERalphaKO (-)/(-) mouse, we show that ERalpha mRNA expression is only decreased by 20% in the arcuate nucleus of the hypothalamus, without a parallel decrease in the VMH, making it a reliable model of pancreas-specific ERalpha elimination. Following exposure to alloxan-induced oxidative stress in vivo, female and male PERalphaKO (-)/(-) mice exhibited a predisposition to beta-cell destruction and insulin deficient diabetes. In male PERalphaKO (-)/(-) mice, exposure to E2 partially prevented alloxan-induced beta-cell destruction and diabetes. ERalpha mRNA expression was induced by hyperglycemia in vivo in islets from young mice as well as in cultured rat islets. The induction of ERalpha mRNA by hyperglycemia was retained in insulin receptor-deficient beta-cells, demonstrating independence from direct insulin regulation. These findings suggest that induction of ERalpha expression acts to naturally protect beta-cells against oxidative injury.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=24498408&dopt=Abstract">Link to Article in PubMed</a>
dc.rights© 2014 Kilic et al. This is an open-access article distributed under the terms of the <a href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</a>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectCellular and Molecular Physiology
dc.subjectEndocrine System Diseases
dc.subjectEndocrinology
dc.subjectEndocrinology, Diabetes, and Metabolism
dc.subjectHormones, Hormone Substitutes, and Hormone Antagonists
dc.titleThe islet estrogen receptor-alpha is induced by hyperglycemia and protects against oxidative stress-induced insulin-deficient diabetes
dc.typeJournal Article
dc.source.journaltitlePloS one
dc.source.volume9
dc.source.issue2
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1435&amp;context=faculty_pubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/436
dc.identifier.contextkey6251714
refterms.dateFOA2022-08-23T15:57:25Z
html.description.abstract<p>The female steroid, 17beta-estradiol (E2), is important for pancreatic beta-cell function and acts via at least three estrogen receptors (ER), ERalpha, ERbeta, and the G-protein coupled ER (GPER). Using a pancreas-specific ERalpha knockout mouse generated using the Cre-lox-P system and a Pdx1-Cre transgenic line (PERalphaKO (-)/(-)), we previously reported that islet ERalpha suppresses islet glucolipotoxicity and prevents beta-cell dysfunction induced by high fat feeding. We also showed that E2 acts via ERalpha to prevent beta-cell apoptosis in vivo. However, the contribution of the islet ERalpha to beta-cell survival in vivo, without the contribution of ERalpha in other tissues is still unclear. Using the PERalphaKO (-)/(-) mouse, we show that ERalpha mRNA expression is only decreased by 20% in the arcuate nucleus of the hypothalamus, without a parallel decrease in the VMH, making it a reliable model of pancreas-specific ERalpha elimination. Following exposure to alloxan-induced oxidative stress in vivo, female and male PERalphaKO (-)/(-) mice exhibited a predisposition to beta-cell destruction and insulin deficient diabetes. In male PERalphaKO (-)/(-) mice, exposure to E2 partially prevented alloxan-induced beta-cell destruction and diabetes. ERalpha mRNA expression was induced by hyperglycemia in vivo in islets from young mice as well as in cultured rat islets. The induction of ERalpha mRNA by hyperglycemia was retained in insulin receptor-deficient beta-cells, demonstrating independence from direct insulin regulation. These findings suggest that induction of ERalpha expression acts to naturally protect beta-cells against oxidative injury.</p>
dc.identifier.submissionpathfaculty_pubs/436
dc.contributor.departmentDepartment of Medicine, Division of Diabetes
dc.source.pagese87941


Files in this item

Thumbnail
Name:
journal.pone.0087941.pdf
Size:
6.371Mb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record

© 2014 Kilic et al. This is an open-access article distributed under the terms of the <a href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</a>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Except where otherwise noted, this item's license is described as © 2014 Kilic et al. This is an open-access article distributed under the terms of the <a href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</a>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.