Alonso-Magdalena Paloma, Ropero Ana B, Carrera M Pilar, Cederroth Christopher R, Baquié Mathurin, Gauthier Benoit R, Nef Serge, Stefani Enrico, Nadal Angel
Instituto de Bioingeniería, Universidad Miguel Hernández de Elche, Alicante, Spain.
PLoS One. 2008 Apr 30;3(4):e2069. doi: 10.1371/journal.pone.0002069.
The function of pancreatic beta-cells is the synthesis and release of insulin, the main hormone involved in blood glucose homeostasis. Estrogen receptors, ER alpha and ER beta, are important molecules involved in glucose metabolism, yet their role in pancreatic beta-cell physiology is still greatly unknown. In this report we show that both ER alpha and ER beta are present in pancreatic beta-cells. Long term exposure to physiological concentrations of 17beta-estradiol (E2) increased beta-cell insulin content, insulin gene expression and insulin release, yet pancreatic beta-cell mass was unaltered. The up-regulation of pancreatic beta-cell insulin content was imitated by environmentally relevant doses of the widespread endocrine disruptor Bisphenol-A (BPA). The use of ER alpha and ER beta agonists as well as ER alphaKO and ER betaKO mice suggests that the estrogen receptor involved is ER alpha. The up-regulation of pancreatic insulin content by ER alpha activation involves ERK1/2. These data may be important to explain the actions of E2 and environmental estrogens in endocrine pancreatic function and blood glucose homeostasis.
胰腺β细胞的功能是合成和释放胰岛素，胰岛素是参与血糖稳态的主要激素。雌激素受体，即雌激素受体α（ERα）和雌激素受体β（ERβ），是参与葡萄糖代谢的重要分子，但其在胰腺β细胞生理学中的作用仍不清楚。在本报告中，我们发现胰腺β细胞中同时存在ERα和ERβ。长期暴露于生理浓度的17β-雌二醇（E2）可增加β细胞胰岛素含量、胰岛素基因表达和胰岛素释放，但胰腺β细胞数量未改变。环境相关剂量的广泛存在的内分泌干扰物双酚A（BPA）可模拟胰腺β细胞胰岛素含量的上调。使用ERα和ERβ激动剂以及ERα基因敲除（ERαKO）和ERβ基因敲除（ERβKO）小鼠表明，所涉及的雌激素受体是ERα。通过激活ERα上调胰腺胰岛素含量涉及细胞外信号调节激酶1/2（ERK1/2）。这些数据对于解释E2和环境雌激素在胰腺内分泌功能和血糖稳态中的作用可能很重要。
