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ISLET CELL ELECTRICAL PACEMAKER MECHANISMS

胰岛细胞电起搏器机制

基本信息

批准号：
3151967
负责人：
DANIEL L COOK
金额：
$ 11.27万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
1983
资助国家：
美国
起止时间：
1983-07-01 至 1986-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3151967
关键词：
calcium metabolism cell membrane cyclic AMP electronic stimulator glucose hormone regulation /control mechanism insulin ion transport membrane permeability pancreatic islet function

项目摘要

Glucose-induced insulin release, a process known to be impaired in diabetes mellitus, involves a cascade of membrane electrical events, controlled by glucose, leading to the uptake of calcium ions trigger insulin release. Each electrical event is due to the gating of electrically charged ion flows across the cell membrane through specific ion conductance "channels". The channels carrying the calcium ions interact periodically and reciprocally with channels carrying potassium ions. Glucose is postulated to control calcium uptake by controlling the potassium channels. We have, therefore, established in our laboratory the recently developed "patch-clamp" method for studying single ionic channels in cell membranes. With this method we propose to 1) identify postassium channels in islet cell membranes and characterize their ionic and voltage dependence, 2) characterize the ability of glucose and certain glucose metabolites to control the activation of these potassium channels. Furthermore, we propose to relate the events at the cell membrane level to the activity of the whole cell in two ways. First, we have hypothesized that the periodicity of calcium and potassium channel activation depends, in large part, on the ability of the cell to buffer the periodic inflow of calcium. We propose to test this by measuring whole cell electrical responses to cyclic AMP, an endogenous agent known to interface with cellular calcium buffering. Second, we propose to determine the degree of coupling between the cellular calcium pool which controls insulin release and the pool which receives the gated calcium influx.

葡萄糖诱导的胰岛素释放，这是一个已知在糖尿病中受损的过程糖尿病，涉及一连串的膜电事件，由葡萄糖，导致钙离子的摄取，引发胰岛素的释放。每一次电子事件都是由于带电离子的选通。通过特定的离子电导流过细胞膜 “频道”。携带钙离子的通道周期性地相互作用并与携带钾离子的通道相互作用。葡萄糖是推测通过控制钾来控制钙的吸收频道。因此，我们最近在实验室建立了研究细胞内单个离子通道的膜片钳方法膜。利用这种方法，我们提出了1)识别钾离子通道并对其离子和电压进行了表征依赖性，2)表征葡萄糖和某些葡萄糖的能力代谢产物来控制这些钾通道的激活。此外，我们建议将细胞膜水平上的事件与整个细胞的活动有两种方式。首先，我们假设钙钾通道激活的周期性取决于，在很大程度上，取决于细胞缓冲周期性流入的能力钙。我们建议通过测量整个细胞的电流来测试这一点。对环磷酸腺苷的反应，环磷酸腺苷是一种已知与之相互作用的内源性因子细胞钙缓冲。第二，我们建议确定控制胰岛素释放的细胞钙池之间的偶联和接受门控钙内流的水池。