Inositol hexakisphosphate and β-cell stimulus-secretion coupling

Christopher J. Barker, Per Olof Berggren

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Inositol hexakisphosphate (InsP6) inhibits serine/threonine protein phosphatases type-1 (PP1), type-2A (PP2A) and type-3 (PP3) in a concentration-dependent manner. Since the activity of voltage-gated L-type Ca2+-channels is increased by inhibition of serine/threonine protein phosphatases, this may explain trhe increased Ca2+-channel activity obtained in the presence of InsP6. In insulin-secreting cells, InsP6 is therefore likely to be one of the key elements modulating Ca2+-influx over the plasma membrane. InsP6 can also modulate insulin exocytosis in permeabilized cells. Concentrations of InsP6 above 20 μM stimulated insulin secretion at basal Ca2+-concentration (30 nM) and primed Ca2+-induced exocytosis (10 μM), both effects being due to activation of PKC. Hence, InsP6 can play an important modulatory role in the regulation of insulin exocytosis and the specific role may then be to recruit secretory granules to the site of exocytosis. The fact that some InsP6 is localised to membranes, so being topographically disposed to regulate ion channels as well as exocytosis, and that it has a rapid rate of turnover in glucose-stimulated insulin-secreting cells, suggest novel functions for InsP6 in the insulin secretory process.

Original languageEnglish (US)
Pages (from-to)3737-3741
Number of pages5
JournalAnticancer research
Volume19
Issue number5 A
StatePublished - Dec 23 1999

Keywords

  • β-cells
  • Ca metabolism
  • Inositol hexakisphosphate
  • Insulin secretion
  • L-type Ca channel
  • Review
  • Stimulus secretion coupling

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Barker, C. J., & Berggren, P. O. (1999). Inositol hexakisphosphate and β-cell stimulus-secretion coupling. Anticancer research, 19(5 A), 3737-3741.