Neuronal calcium sensor-1 potentiates glucose-dependent exocytosis in pancreatic β cells through activation of phosphatidylinositol 4-kinase β

Jesper Gromada, Christina Bark, Kamille Smidt, Alexander M. Efanov, Juliette Janson, Slavena A. Mandic, Dominic Luc Webb, Wei Zhang, Björn Meister, Andreas Jeromin, Per Olof Berggren

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Cytosolic free Ca2+ plays an important role in the molecular mechanisms leading to regulated insulin secretion by the pancreatic β 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 β 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 β 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 β cells. Our results provide evidence for an essential role of phosphoinositide synthesis in the regulation of glucose-induced insulin secretion by the pancreatic β cell. We also demonstrate that NCS-1 and its downstream target, PI 4-kinase β;, are critical players in this process by virtue of their capacity to regulate the release competence of the secretory granules.

Original languageEnglish (US)
Pages (from-to)10303-10308
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number29
DOIs
StatePublished - Jul 19 2005

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Keywords

  • Ca-dependent activator protein for secretion
  • Insulin
  • Islet
  • Phosphoinositides
  • Secretion

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Gromada, J., Bark, C., Smidt, K., Efanov, A. M., Janson, J., Mandic, S. A., Webb, D. L., Zhang, W., Meister, B., Jeromin, A., & Berggren, P. O. (2005). Neuronal calcium sensor-1 potentiates glucose-dependent exocytosis in pancreatic β cells through activation of phosphatidylinositol 4-kinase β. Proceedings of the National Academy of Sciences of the United States of America, 102(29), 10303-10308. https://doi.org/10.1073/pnas.0504487102