%0 Journal Article
%T The Islet Estrogen Receptor-¦Á Is Induced by Hyperglycemia and Protects Against Oxidative Stress-Induced Insulin-Deficient Diabetes
%A Gamze Kilic
%A Ana I. Alvarez-Mercado
%A Bader Zarrouki
%A Darren Opland
%A Chong Wee Liew
%A Laura C. Alonso
%A Martin G. Myers
%A Jean-Christophe Jonas
%A Vincent Poitout
%A Rohit N. Kulkarni
%A Franck Mauvais-Jarvis
%J PLOS ONE
%D 2014
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0087941
%X The female steroid, 17¦Â-estradiol (E2), is important for pancreatic ¦Â-cell function and acts via at least three estrogen receptors (ER), ER¦Á, ER¦Â, and the G-protein coupled ER (GPER). Using a pancreas-specific ER¦Á knockout mouse generated using the Cre-lox-P system and a Pdx1-Cre transgenic line (PER¦ÁKO£¿/£¿), we previously reported that islet ER¦Á suppresses islet glucolipotoxicity and prevents ¦Â-cell dysfunction induced by high fat feeding. We also showed that E2 acts via ER¦Á to prevent ¦Â-cell apoptosis in vivo. However, the contribution of the islet ER¦Á to ¦Â-cell survival in vivo, without the contribution of ER¦Á in other tissues is still unclear. Using the PER¦ÁKO£¿/£¿ mouse, we show that ER¦Á 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 ER¦Á elimination. Following exposure to alloxan-induced oxidative stress in vivo, female and male PER¦ÁKO£¿/£¿ mice exhibited a predisposition to ¦Â-cell destruction and insulin deficient diabetes. In male PER¦ÁKO£¿/£¿ mice, exposure to E2 partially prevented alloxan-induced ¦Â-cell destruction and diabetes. ER¦Á mRNA expression was induced by hyperglycemia in vivo in islets from young mice as well as in cultured rat islets. The induction of ER¦Á mRNA by hyperglycemia was retained in insulin receptor-deficient ¦Â-cells, demonstrating independence from direct insulin regulation. These findings suggest that induction of ER¦Á expression acts to naturally protect ¦Â-cells against oxidative injury.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0087941