Requirement of inositol pyrophosphates for full exocytotic capacity in pancreatic β cells

Christopher Illies, Jesper Gromada, Roberta Fiume, Barbara Leibiger, Jia Yu, Kirstine Juhl, Shao Nian Yang, Deb K. Barma, John R. Falck, Adolfo Saiardi, Christopher J. Barker, Per Olof Berggren

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124 Scopus citations

Abstract

Inositol pyrophosphates are recognized components of cellular processes that regulate vesicle trafficking, telomere length, and apoptosis. We observed that pancreatic β cells maintain high basal concentrations of the pyrophosphate diphosphoinositol pentakisphosphate (InsP7 or IP 7). Inositol hexakisphosphate kinases (IP6Ks) that can generate IP7 were overexpressed. This overexpression stimulated exocytosis of insulin-containing granules from the readily releasable pool. Exogenously applied IP7 dose-dependently enhanced exocytosis at physiological concentrations. We determined that IP6K1 and IP6K2 were present in β cells. RNA silencing of IP6K1, but not IP6K2, inhibited exocytosis, which suggests that IP6K1 is the critical endogenous kinase. Maintenance of high concentrations of IP7 in the pancreatic β cell may enhance the immediate exocytotic capacity and consequently allow rapid adjustment of insulin secretion in response to increased demand.

Original languageEnglish (US)
Pages (from-to)1299-1302
Number of pages4
JournalScience
Volume318
Issue number5854
DOIs
StatePublished - Nov 23 2007

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    Illies, C., Gromada, J., Fiume, R., Leibiger, B., Yu, J., Juhl, K., Yang, S. N., Barma, D. K., Falck, J. R., Saiardi, A., Barker, C. J., & Berggren, P. O. (2007). Requirement of inositol pyrophosphates for full exocytotic capacity in pancreatic β cells. Science, 318(5854), 1299-1302. https://doi.org/10.1126/science.1146824