Pancreatic insulin content regulation by the estrogen receptor ER alpha

Abstract

The function of pancreatic b-cells is the synthesis and release of insulin, the main hormone involved in blood glucose homeostasis. Estrogen receptors, ERa and ERb, are important molecules involved in glucose metabolism, yet their role in pancreatic b-cell physiology is still greatly unknown. In this report we show that both ERa and ERb are present in pancreatic b-cells. Long term exposure to physiological concentrations of 17b-estradiol (E2) increased b-cell insulin content, insulin gene expression and insulin release, yet pancreatic b-cell mass was unaltered. The up-regulation of pancreatic b-cell insulin content was imitated by environmentally relevant doses of the widespread endocrine disruptor Bisphenol-A (BPA). The use of ERa and ERb agonists as well as ERaKO and ERbKO mice suggests that the estrogen receptor involved is ERa. The upregulation of pancreatic insulin content by ERa 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.