Rapid insulinotropic effect of 17β-estradiol via a plasma membrane receptor

Impaired insulin secretion is a hallmark in both type I and type II diabetic individuals. Whereas type I (insulin-dependent diabetes mellitus) implies p-cen destruction, type II (non-insulin dependent diabetes mellitus), responsible for 75% of diabetic syndromes, involves diminished glucose-dependent secretion of insulin from pancreatic beta-cells. Although a clear demonstration of a direct effect of 17 beta-estradiol on the pancreatic P-cen is lacking, an in vivo insulinotropic effect has been suggested. In this report we describe the effects of 17 beta-estradiol in mouse pancreatic p-cells. 17 beta-Estradiol, at physiological concentrations, closes K-ATP channels, which are also targets for antidiabetic sulfonylureas, in a rapid and reversible manner. Furthermore, in synergy with glucose, 17 beta-estradiol depolarizes the plasma membrane, eliciting electrical activity and intracellular calcium signals, which in turn enhance insulin secretion. These effects occur through a receptor located at the plasma membrane, distinct from the classic cytosolic estrogen receptor. Specific competitive binding and localization of 17 beta-estradiol receptors at the plasma membrane was demonstrated using confocal reflective microscopy and immunocytochemistry. Gaining deeper knowledge of the effect induced by 17 beta-estradiol may be important in order to better understand the hormonal regulation of insulin secretion and for the treatment of NIDDM.