The estrogenic effect of bisphenol A disrupts pancreatic beta-cell function in vivo and induces insulin resistance

The function of the pancreatic beta-cell is the storage and release of insulin, the main hormone involved in blood glucose homeostasis. The results in this article show that the widespread environmental contaminant bisphenol-A (BPA) imitates 17 beta-estfadiol (E-2) effects in vivo on blood glucose homeostasis through genomic and nongenomic pathways. The exposure of adult mice to a single low dose (10 mu g/kg) of either E-2 or BPA induces a rapid decrease in glycemia that correlates with a rise of plasma insulin. Longer exposures to E-2 and BPA induce an increase in pancreatic beta-cell insulin content in an estrogen-receptor-dependent manner. This effect is visible after 2 days of treatment and starting at doses as low as 10 mu g/kg/day. After 4 days of treatment with either E-2 or BPA, these mice developed chronic hyperinsulinemia, and their glucose and insulin tolerance tests were altered. These experiments unveil the link between environmental estrogens and insulin resistance. Therefore, either abnormal levels of endogenous estrogens or environmental estrogen exposure enhances the risk of developing type 2 diabetes mellitus, hypertension, and dyslipidemia.