文章基本信息

标题：Microfluidic glucose stimulation reveals limited coordination of intracellular Ca2+ activity oscillations in pancreatic islets
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作者：Jonathan V. Rocheleau ; Glenn M. Walker ; W. Steven Head 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：35
页码：12899-12903
DOI：10.1073/pnas.0405149101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The pancreatic islet is a functional microorgan involved in maintaining normoglycemia through regulated secretion of insulin and other hormones. Extracellular glucose stimulates insulin secretion from islet {beta} cells through an increase in redox state, which can be measured by NAD(P)H autofluorescence. Glucose concentrations over {approx}7 mM generate synchronous oscillations in {beta} cell intracellular Ca2+ concentration ([Ca2+]i), which lead to pulsatile insulin secretion. Prevailing models assume that the pancreatic islet acts as a functional syncytium, and the whole islet [Ca2+]i response has been modeled in terms of islet bursting and pacemaker models. To test these models, we developed a microfluidic device capable of partially stimulating an islet, while allowing observation of the NAD(P)H and [Ca2+]i responses. We show that {beta} cell [Ca2+]i oscillations occur only within regions stimulated with more than {approx}6.6 mM glucose. Furthermore, we show that tolbutamide, an antagonist of the ATP-sensitive K+ channel, allows these oscillations to travel farther into the nonstimulated regions of the islet. Our approach shows that the extent of Ca2+ propagation across the islet depends on a delicate interaction between the degree of coupling and the extent of ATP-sensitive K+-channel activation and illustrates an experimental paradigm that will have utility for many other biological systems.
关键词：β cell ; ATP-sensitive K+ channels ; NAD(P)H