Increase in cellular glutamate levels stimulates exocytosis in pancreatic β-cells

Marianne Hoy, Pierre Maechler, Alexander M. Efanov, Claes B. Wollheim, Per Olof Berggren, Jesper Gromada

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

Glutamate has been implicated as an intracellular messenger in the regulation of insulin secretion in response to glucose. Here we demonstrate by measurements of cell capacitance in rat pancreatic β-cells that glutamate (1 mM) enhanced Ca2+-dependent exocytosis. Glutamate (1 mM) also stimulated insulin secretion from permeabilized rat β-cells. The effect was dose-dependent (half-maximum at 5.1 mM) and maximal at 10 mM glutamate. Glutamate-induced exocytosis was stronger in rat β-cells and clonal INS-1E cells compared to β-cells isolated from mice and in parental INS-1 cells, which correlated with the expressed levels of glutamate dehydrogenase. Glutamate-induced exocytosis was inhibited by the protonophores FCCP and SF6847, by the vacuolar-type H+-ATPase inhibitor bafilomycin A1 and by the glutamate transport inhibitor Evans Blue. Our data provide evidence that exocytosis in β-cells can be modulated by physiological increases in cellular glutamate levels. The results suggest that stimulation of exocytosis is associated with accumulation of glutamate in the secretory granules, a process that is dependent on the transgranular proton gradient.

Original languageEnglish (US)
Pages (from-to)199-203
Number of pages5
JournalFEBS letters
Volume531
Issue number2
DOIs
StatePublished - Nov 6 2002

Keywords

  • Beta cell
  • Exocytosis
  • Glutamate
  • Insulin

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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    Hoy, M., Maechler, P., Efanov, A. M., Wollheim, C. B., Berggren, P. O., & Gromada, J. (2002). Increase in cellular glutamate levels stimulates exocytosis in pancreatic β-cells. FEBS letters, 531(2), 199-203. https://doi.org/10.1016/S0014-5793(02)03500-7