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

Research output: Contribution to journalArticle

116 Citations (Scopus)

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

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Diphosphates
Exocytosis
Inositol
Insulin
Telomere
RNA Interference
Phosphotransferases
Apoptosis

ASJC Scopus subject areas

  • General

Cite this

Illies, C., Gromada, J., Fiume, R., Leibiger, B., Yu, J., Juhl, K., ... 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

Requirement of inositol pyrophosphates for full exocytotic capacity in pancreatic β cells. / Illies, Christopher; Gromada, Jesper; Fiume, Roberta; Leibiger, Barbara; Yu, Jia; Juhl, Kirstine; Yang, Shao Nian; Barma, Deb K.; Falck, John R.; Saiardi, Adolfo; Barker, Christopher J.; Berggren, Per Olof.

In: Science, Vol. 318, No. 5854, 23.11.2007, p. 1299-1302.

Research output: Contribution to journalArticle

Illies, C, Gromada, J, Fiume, R, Leibiger, B, Yu, J, Juhl, K, Yang, SN, Barma, DK, Falck, JR, Saiardi, A, Barker, CJ & Berggren, PO 2007, 'Requirement of inositol pyrophosphates for full exocytotic capacity in pancreatic β cells', Science, vol. 318, no. 5854, pp. 1299-1302. https://doi.org/10.1126/science.1146824
Illies C, Gromada J, Fiume R, Leibiger B, Yu J, Juhl K et al. Requirement of inositol pyrophosphates for full exocytotic capacity in pancreatic β cells. Science. 2007 Nov 23;318(5854):1299-1302. https://doi.org/10.1126/science.1146824
Illies, Christopher ; Gromada, Jesper ; Fiume, Roberta ; Leibiger, Barbara ; Yu, Jia ; Juhl, Kirstine ; Yang, Shao Nian ; Barma, Deb K. ; Falck, John R. ; Saiardi, Adolfo ; Barker, Christopher J. ; Berggren, Per Olof. / Requirement of inositol pyrophosphates for full exocytotic capacity in pancreatic β cells. In: Science. 2007 ; Vol. 318, No. 5854. pp. 1299-1302.
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