Type 2 diabetes (T2D), results from a deficiency in insulin action on peripheral tissues together with a lack of compensatory insulin production and release by pancreatic beta cells. The etiology of T2D involves both, genetic predisposition and environmental factors. Bisphenol-A (BPA) is a widespread endocrine disrupting chemical that modify pancreatic beta cell function and induce insulin resistance in rodents after treatment during different timing of exposure, including pregnancy. This is a sensitive period of susceptibility for both mothers and offspring. Epidemiological studies associate BPA levels in urine with T2D development in adult humans. Adult male mouse treatment with low doses of BPA induces insulin resistance and hyperinsulinemia. Experiments using isolated beta cells as well as whole islet of Langerhans, suggest that BPA acts directly in beta cells to increase insulin content and release. Insulin content regulation by BPA is an estrogen receptor alpha (ERα) dependent process. In addition, BPA regulates beta cell electrical activity via a pathway which involves estrogen receptors β (ERβ). Electrophysiological measurements showed a decrease in sodium, calcium and total potassium currents in BPA-treated islets which is in line with BPA effects on gene expression. BPA-induced changes were abrogated in beta cells derived from ERβ−/− mice, suggesting that ERβ mediates BPA effects on ion channel expression and function in pancreatic beta cells.
18 - 21 May 2019
European Society of Endocrinology