The islet estrogen receptor-alpha is induced by hyperglycemia and protects against oxidative stress-induced insulin-deficient diabetes
Alvarez-Mercado, Ana I.
Liew, Chong Wee
Alonso, Laura C.
Myers Jr, Martin G.
Kulkarni, Rohit N.
UMass Chan AffiliationsDepartment of Medicine, Division of Diabetes
Document TypeJournal Article
KeywordsCellular and Molecular Physiology
Endocrine System Diseases
Endocrinology, Diabetes, and Metabolism
Hormones, Hormone Substitutes, and Hormone Antagonists
MetadataShow full item record
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.
SourcePLoS One. 2014 Feb 3;9(2):e87941. doi: 10.1371/journal.pone.0087941. eCollection 2014. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/30192
Related ResourcesLink to Article in PubMed
Rights© 2014 Kilic et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, 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.