文章基本信息

标题：Neuronal calcium sensor-1 potentiates glucose-dependent exocytosis in pancreatic β cells through activation of phosphatidylinositol 4-kinase β
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作者：Jesper Gromada ; Christina Bark ; Kamille Smidt 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：2005
卷号：102
期号：29
页码：10303-10308
DOI：10.1073/pnas.0504487102
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Cytosolic free Ca2+ plays an important role in the molecular mechanisms leading to regulated insulin secretion by the pancreatic {beta} cell. A number of Ca2+-binding proteins have been implicated in this process. Here, we define the role of the Ca2+-binding protein neuronal Ca2+ sensor-1 (NCS-1) in insulin secretion. In pancreatic {beta} cells, NCS-1 increases exocytosis by promoting the priming of secretory granules for release and increasing the number of granules residing in the readily releasable pool. The effect of NCS-1 on exocytosis is mediated through an increase in phosphatidylinositol (PI) 4-kinase {beta} activity and the generation of phosphoinositides, specifically PI 4-phosphate and PI 4,5-bisphosphate. In turn, PI 4,5-bisphosphate controls exocytosis through the Ca2+-dependent activator protein for secretion present in {beta} cells. Our results provide evidence for an essential role of phosphoinositide synthesis in the regulation of glucose-induced insulin secretion by the pancreatic {beta} cell. We also demonstrate that NCS-1 and its downstream target, PI 4-kinase {beta
关键词：insulin ; phosphoinositides ; islet ; secretion ; Ca2+-dependent activator protein for secretion