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

The estrogen receptor ER alpha is emerging as a key molecule involved in glucose and lipid metabolism. The main functions of pancreatic P-cells are the biosynthesis and release of insulin, the only hormone that can directly decrease blood glucose levels. Estrogen receptors ER alpha and ER beta exist in beta-cells. The role of ER beta is still unknown, yet ER alpha plays an important role in the regulation of insulin biosynthesis, insulin secretion and P-cell survival. Activation of ER alpha by 17 beta-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 ER alpha by physiological concentrations of E2 may play an important role in the adaptation of the endocrine pancreas to pregnancy. However, if ER alpha 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 beta-cell exhaustion and therefore, it may contribute to the development of type II diabetes. (C) 2009 Elsevier Ireland Ltd. All rights reserved.