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

Abstract

Impaired insulin secretion is a hallmark in both type I and type II diabetic individuals. Whereas type I (insulin‐dependent diabetes mellitus) implies β‐cell destruction, type II (non‐insulin dependent diabetes mellitus), responsible for 75% of diabetic syndromes, involves diminished glucose‐dependent secretion of insulin from pancreatic β‐cells. Although a clear demonstration of a direct effect of 17β‐estradiol on the pancreatic β‐cell is lacking, an in vivo insulinotropic effect has been suggested. In this report we describe the effects of 17β‐estradiol in mouse pancreatic β‐cells. 17β‐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, 17β‐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 17β‐estradiol receptors at the plasma membrane was demonstrated using confocal reflective microscopy and immunocytochemistry. Gaining deeper knowledge of the effect induced by 17β‐estradiol may be important in order to better understand the hormonal regulation of insulin secretion and for the treatment of NIDDM.— Nadal, A., Rovira, J. M., Laribi, O., Leon‐Quinto, T., Andreu, E., Ripoll, C., Soria, B. Rapid insulinotropic effect of 17b‐estradiol via a plasma membrane receptor. FASEB J. 12, 1341–1348 (1998)