Nadal A, Rovira J M, Laribi O, Leon-quinto T, Andreu E, Ripoll C, Soria B
Institute of Bioengineering and Department of Physiology, Miguel Hernández University, San Juan Campus, Alicante, Spain.
FASEB J. 1998 Oct;12(13):1341-8. doi: 10.1096/fasebj.12.13.1341.
Impaired insulin secretion is a hallmark in both type I and type II diabetic individuals. Whereas type I (insulin-dependent diabetes mellitus) implies ss-cell 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 17beta-estradiol on the pancreatic ss-cell is lacking, an in vivo insulinotropic effect has been suggested. In this report we describe the effects of 17beta-estradiol in mouse pancreatic ss-cells. 17beta-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, 17beta-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 17beta-estradiol receptors at the plasma membrane was demonstrated using confocal reflective microscopy and immunocytochemistry. Gaining deeper knowledge of the effect induced by 17beta-estradiol may be important in order to better understand the hormonal regulation of insulin secretion and for the treatment of NIDDM. receptor.
胰岛素分泌受损是I型和II型糖尿病患者的一个标志。I型（胰岛素依赖型糖尿病）意味着β细胞被破坏，而II型（非胰岛素依赖型糖尿病）占糖尿病综合征的75%，涉及胰腺β细胞葡萄糖依赖性胰岛素分泌减少。虽然缺乏17β-雌二醇对胰腺β细胞直接作用的明确证据，但已有人提出其在体内具有促胰岛素分泌作用。在本报告中，我们描述了17β-雌二醇对小鼠胰腺β细胞的作用。生理浓度的17β-雌二醇能快速、可逆地关闭K(ATP)通道，该通道也是抗糖尿病磺脲类药物的作用靶点。此外，17β-雌二醇与葡萄糖协同作用，使质膜去极化，引发电活动和细胞内钙信号，进而增强胰岛素分泌。这些作用是通过位于质膜上的一种受体实现的，该受体不同于经典的胞质雌激素受体。利用共聚焦反射显微镜和免疫细胞化学技术证实了17β-雌二醇受体在质膜上的特异性竞争性结合和定位。深入了解17β-雌二醇所诱导的作用对于更好地理解胰岛素分泌的激素调节以及治疗非胰岛素依赖型糖尿病可能具有重要意义。受体。
