Suppr超能文献

可视化胰岛素分泌。2004年闵可夫斯基讲座

Visualising insulin secretion. The Minkowski Lecture 2004.

作者信息

Rutter G A

机构信息

Henry Wellcome Laboratories for Integrated Cell Signalling, School of Medical Sciences, University of Bristol, Bristol, UK.

出版信息

Diabetologia. 2004 Nov;47(11):1861-72. doi: 10.1007/s00125-004-1541-1. Epub 2004 Nov 17.

Abstract

Insulin secretion from pancreatic islet beta cells is a tightly regulated process, under the close control of blood glucose concentrations, neural inputs and circulating hormones. Defects in glucose-triggered insulin secretion, possibly exacerbated by a decrease in beta cell mass, are ultimately responsible for the development of type 2 diabetes. A full understanding of the mechanisms by which glucose and other nutrients trigger insulin secretion will probably be essential to allow for the development of new therapies of type 2 diabetes and for the derivation of "artificial" beta cells from embryonic stem cells as a treatment for type 1 diabetes. I focus here on recent developments in our understanding of beta cell glucose sensing, achieved in part through the development of recombinant targeted probes (luciferase, green fluorescent protein) that allow islet beta cell metabolism and Ca(2+) handling to be imaged in situ in the intact islet with single cell resolution. Combined with classical biochemistry, these techniques show that the beta cell is uniquely poised, thanks to the expression of low levels of lactate dehydrogenase and plasma membrane lactate/monocarboxylate transporters, to channel glucose carbons towards oxidative metabolism, ATP synthesis and inhibition of AMP-activated protein kinase, a newly defined regulator of insulin release. I also discuss the molecular basis of the recruitment of secretory vesicles to the cell surface, analysed by the use of new imaging techniques including total internal reflection of fluorescence, as well as the "nanomechanics" of the exocytotic event itself.

摘要

胰腺胰岛β细胞分泌胰岛素是一个受到严格调控的过程,处于血糖浓度、神经输入和循环激素的密切控制之下。葡萄糖触发的胰岛素分泌缺陷,可能因β细胞数量减少而加剧,最终导致2型糖尿病的发生。全面了解葡萄糖和其他营养物质触发胰岛素分泌的机制,对于开发2型糖尿病的新疗法以及从胚胎干细胞中衍生出“人工”β细胞以治疗1型糖尿病可能至关重要。我在此重点介绍我们对β细胞葡萄糖感应的最新认识进展,这部分是通过开发重组靶向探针(荧光素酶、绿色荧光蛋白)实现的,这些探针能够以单细胞分辨率在完整胰岛中原位成像胰岛β细胞的代谢和Ca(2+)处理情况。结合经典生物化学,这些技术表明,由于低水平乳酸脱氢酶和质膜乳酸/单羧酸转运体的表达,β细胞处于独特的状态,能够将葡萄糖碳导向氧化代谢、ATP合成并抑制AMP激活的蛋白激酶,这是一种新定义的胰岛素释放调节因子。我还讨论了利用包括荧光全内反射在内的新成像技术分析分泌囊泡募集到细胞表面的分子基础,以及胞吐事件本身的“纳米力学”。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验