Diphosphoinositol pentakisphosphate as a novel mediator of insulin exocytosis

Christopher J. Barker, Christopher Illies, Roberta Fiume, Gian Carlo Gaboardi, Jia Yu, Per Olof Berggren

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The pancreatic β-cell has served as an important model system for the revelation of new physiological roles for inositides. Initially, our studies were restricted to the role of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) in the regulation of cytoplasmic free calcium concentration ([Ca2+]i), but it soon became clear that other inositol phosphates could also regulate β-cell [Ca2+]i. For example, inositol hexakisphosphate (InsP6) promotes the opening of the key voltage-dependent L-type Ca2+ channels, responsible for Ca2+ influx and the final release of insulin. Furthermore, InsP6 and inositol lipids such as phosphatidylinositol 4,5-bisphosphate are intimately involved the regulation of endocytosis and exocytosis. We now review our most recent work, which has focused on the phosphorylation product of InsP6, diphosphoinositol pentakisphosphate (PP-InsP5 or InsP7). We have established that InsP7 via the activity of the InsP6 kinase, IP6K1, promotes insulin release from the readily releasable pool of vesicles (RRP). The RRP is thought to be synonymous with the first phase of insulin secretion. This has a direct implication for type 2 diabetes, as it is this initial phase of insulin release that is curtailed in the disease. Hints from human genetic linkage studies suggest that disruption of IP6K1 could be a factor in the development of type 2 diabetes and a recent mouse model, where IP6K1 is universally deleted, exhibits lowered plasma insulin levels. Hence, this is yet another important example demonstrating how the β-cell utilizes inositides in the regulation of function. Although we do not fully understand the underlying molecular mechanisms, it is clear that IP6K1-mediated production of InsP7 has an essential role in the regulation of the insulin secretory process.

Original languageEnglish
Pages (from-to)168-173
Number of pages6
JournalAdvances in Enzyme Regulation
Volume49
Issue number1
DOIs
StatePublished - Jun 10 2009
Externally publishedYes

Fingerprint

Exocytosis
Insulin
Type 2 Diabetes Mellitus
Phytic Acid
Genetic Linkage
Inositol 1,4,5-Trisphosphate
Inositol Phosphates
Secretory Pathway
Medical Genetics
Inositol
Phosphatidylinositols
Endocytosis
1-diphosphoinositol pentakisphosphate
Phosphotransferases
Phosphorylation
Calcium
Lipids
inositol heptakisphosphate

ASJC Scopus subject areas

  • Molecular Medicine
  • Cancer Research
  • Genetics
  • Molecular Biology

Cite this

Barker, C. J., Illies, C., Fiume, R., Gaboardi, G. C., Yu, J., & Berggren, P. O. (2009). Diphosphoinositol pentakisphosphate as a novel mediator of insulin exocytosis. Advances in Enzyme Regulation, 49(1), 168-173. https://doi.org/10.1016/j.advenzreg.2009.01.001

Diphosphoinositol pentakisphosphate as a novel mediator of insulin exocytosis. / Barker, Christopher J.; Illies, Christopher; Fiume, Roberta; Gaboardi, Gian Carlo; Yu, Jia; Berggren, Per Olof.

In: Advances in Enzyme Regulation, Vol. 49, No. 1, 10.06.2009, p. 168-173.

Research output: Contribution to journalArticle

Barker, CJ, Illies, C, Fiume, R, Gaboardi, GC, Yu, J & Berggren, PO 2009, 'Diphosphoinositol pentakisphosphate as a novel mediator of insulin exocytosis', Advances in Enzyme Regulation, vol. 49, no. 1, pp. 168-173. https://doi.org/10.1016/j.advenzreg.2009.01.001
Barker, Christopher J. ; Illies, Christopher ; Fiume, Roberta ; Gaboardi, Gian Carlo ; Yu, Jia ; Berggren, Per Olof. / Diphosphoinositol pentakisphosphate as a novel mediator of insulin exocytosis. In: Advances in Enzyme Regulation. 2009 ; Vol. 49, No. 1. pp. 168-173.
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