The pancreatic β-cell as a target of estrogens and xenoestrogens: Implications for blood glucose homeostasis and diabetes

The estrogen receptor ERα is emerging as a key molecule involved in glucose and lipid metabolism. The main functions of pancreatic β-cells are the biosynthesis and release of insulin, the only hormone that can directly decrease blood glucose levels. Estrogen receptors ERα and ERβ exist in β-cells. The role of ERβ is still unknown, yet ERα plays an important role in the regulation of insulin biosynthesis, insulin secretion and β-cell survival. Activation of ERα by 17β-estradiol (E2) and the environmental estrogen bisphenol-A (BPA) promotes an increase of insulin biosynthesis through a non-classical estrogen-activated pathway that involves phosphorylation of ERK1/2. The activation of ERα by physiological concentrations of E2 may play an important role in the adaptation of the endocrine pancreas to pregnancy. However, if ERα is over stimulated by an excess of E2 or the action of an environmental estrogen such as BPA, it will produce an excessive insulin signaling. This may provoke insulin resistance in the liver and muscle, as well as β-cell exhaustion and therefore, it may contribute to the development of type II diabetes.