Aim: 

The estrogen receptor ERa is emerging as a key molecule involved in glucose homeostasis. The main functions of pancreatic b-cells are the biosynthesis and release of insulin. Estrogen receptors ERa and ERb exist in b-cells. Our aim is to investigate the role of ERs in b-cell function.

Methods: 

Experiments were performed using OF1 mice and ERaKO and ERbKO mice. Pancreatic insulin content and secretion were measured by RIA. Insulin mRNA by Real Time PCR. Pancreatic b-cell mass by BrdU incorporation and area measurement.

Results: 

Experiments in vivo have demonstrated that equal doses of 17b-estradiol (E2) and the environmental estrogen Bisphenol-A (BPA) (100mg/Kg/day) increase pancreatic insulin content and induce peripheral insulin resistance. Long term exposure in vitro to physiological concentrations of 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 BPA. Using ERaKO and ERbKO mice we have demonstrated that ERa is the receptor involved in E2 and BPA regulation of insulin biosynthesis. PPT, E2 and BPA-increased insulin biosynthesis was abolished by the ERK1/2 blocker PD98059. In addition, PPT rapidly activates ERK1/2.

Conclusions: 

The activation of ERa by E2 may play an important role in the adaptation of the endocrine pancreas to pregnancy. However, if ERa is over stimulated, it will produce excessive insulin signaling that may provoke peripheral insulin resistance as well as b-cell exhaustion and therefore, may contribute to the development of type II diabetes.