RAPID INSULINOTROPIC EFFECT OF 17-BETA-ESTRADIOL VIA A PLASMA-MEMBRANE RECEPTOR

Impaired insulin secretion is a hallmark in both type I and type II di abetic individuals. Whereas type I (insulin-dependent diabetes mellitu s) implies p-cen destruction, type II (non-insulin dependent diabetes mellitus), responsible for 75% of diabetic syndromes, involves diminis hed glucose-dependent secretion of insulin from pancreatic beta-cells. Although a clear demonstration of a direct effect of 17 beta-estradio l 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 physiolo gical concentrations, closes K-ATP channels, which are also targets fo r antidiabetic sulfonylureas, in a rapid and reversible manner. Furthe rmore, in synergy with glucose, 17 beta-estradiol depolarizes the plas ma membrane, eliciting electrical activity and intracellular calcium s ignals, which in turn enhance insulin secretion. These effects occur t hrough a receptor located at the plasma membrane, distinct from the cl assic cytosolic estrogen receptor. Specific competitive binding and lo calization of 17 beta-estradiol receptors at the plasma membrane was d emonstrated using confocal reflective microscopy and immunocytochemist ry. Gaining deeper knowledge of the effect induced by 17 beta-estradio l may be important in order to better understand the hormonal regulati on of insulin secretion and for the treatment of NIDDM.