University of Massachusetts Medical School Faculty Publications
UMMS Affiliation
Department of Medicine, Division of Diabetes
Publication Date
2014-02-03
Document Type
Article
Disciplines
Cellular and Molecular Physiology | Endocrine System Diseases | Endocrinology | Endocrinology, Diabetes, and Metabolism | Hormones, Hormone Substitutes, and Hormone Antagonists
Abstract
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.
Rights and Permissions
© 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.
DOI of Published Version
10.1371/journal.pone.0087941
Source
PLoS One. 2014 Feb 3;9(2):e87941. doi: 10.1371/journal.pone.0087941. eCollection 2014. Link to article on publisher's site
Related Resources
Journal/Book/Conference Title
PloS one
PubMed ID
24498408
Repository Citation
Kilic G, Alvarez-Mercado AI, Zarrouki B, Opland D, Liew CW, Alonso LC, Myers Jr MG, Jonas J, Poitout V, Kulkarni RN, Mauvais-Jarvis F. (2014). The islet estrogen receptor-alpha is induced by hyperglycemia and protects against oxidative stress-induced insulin-deficient diabetes. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1371/journal.pone.0087941. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/436
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Included in
Cellular and Molecular Physiology Commons, Endocrine System Diseases Commons, Endocrinology Commons, Endocrinology, Diabetes, and Metabolism Commons, Hormones, Hormone Substitutes, and Hormone Antagonists Commons