Rapid insulinotropic effect of 17β-estradiol via a plasma membrane receptor
Rapid insulinotropic effect of 17β-estradiol via a plasma membrane receptor
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DOI：
10.1096/fasebj.12.13.1341
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发表时间：
1998-10-01
期刊：
影响因子：
4.8
通讯作者：
Soria, B
中科院分区：
文献类型：
--
作者：
Nadal, A;Rovira, JM;Soria, B
胰岛素分泌受损是I型和II型糖尿病患者的标志。而I型（胰岛素依赖型糖尿病）意味着p-cen的破坏，II型（非胰岛素依赖型糖尿病），负责75%的糖尿病综合征，涉及胰腺β细胞葡萄糖依赖型胰岛素分泌减少。虽然17 -雌二醇对胰腺p -c的直接作用还没有明确的证明，但已经提出了体内胰岛素改善作用。在本报告中，我们描述了17 β -雌二醇在小鼠胰腺p细胞中的作用。在生理浓度下，β -雌二醇以快速和可逆的方式关闭K-ATP通道，K-ATP通道也是抗糖尿病磺脲类药物的靶点。此外，在与葡萄糖的协同作用下，17 β -雌二醇使质膜去极化，引发电活动和细胞内钙信号，进而促进胰岛素分泌。这些作用通过位于质膜的受体发生，不同于经典的细胞质雌激素受体。利用共聚焦反射显微镜和免疫细胞化学证明了17种β -雌二醇受体在质膜上的特异性竞争结合和定位。为了更好地理解胰岛素分泌的激素调节和NIDDM的治疗，深入了解17 -雌二醇诱导的作用可能很重要。
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.