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：2010
卷号：107
期号：14
页码：6465-6470
DOI：10.1073/pnas.0908935107
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Extracellular ATP has been proposed as a paracrine signal in rodent islets, but it is unclear what role ATP plays in human islets. We now show the presence of an ATP signaling pathway that enhances the human {beta} cell's sensitivity and responsiveness to glucose fluctuations. By using in situ hybridization, RT-PCR, immunohistochemistry, and Western blotting as well as recordings of cytoplasmic-free Ca2+ concentration, [Ca2+]i, and hormone release in vitro, we show that human {beta} cells express ionotropic ATP receptors of the P2X3 type and that activation of these receptors by ATP coreleased with insulin amplifies glucose-induced insulin secretion. Released ATP activates P2X3 receptors in the {beta}-cell plasma membrane, resulting in increased [Ca2+]i and enhanced insulin secretion. Therefore, in human islets, released ATP forms a positive autocrine feedback loop that sensitizes the {beta} cell's secretory machinery. This may explain how the human pancreatic {beta} cell can respond so effectively to relatively modest changes in glucose concentration under physiological conditions in vivo.
关键词：extracellular ATP ; human pancreatic β cell ; insulin secretion ; P2X receptor ; positive autocrine feedback
