en
Scientific article
English

Reduction of plasma membrane glutamate transport potentiates insulin but not glucagon secretion in pancreatic islet cells

Published inMolecular and cellular endocrinology, vol. 338, no. 1-2, p. 46-57
Publication date2011
Abstract

Glutamate is generated during nutrient stimulation of pancreatic islets and has been proposed to act both as an intra- and extra-cellular messenger molecule. We demonstrate that glutamate is not co-secreted with the hormones from intact islets or purified α- and β-cells. Fractional glutamate release was 5-50 times higher than hormone secretion. Furthermore, various hormone secretagogues did not elicit glutamate efflux. Interestingly, epinephrine even decreased glutamate release while increasing glucagon secretion. Rather than being co-secreted with hormones, we show that glutamate is mainly released via plasma membrane excitatory amino acid transporters (EAAT) by uptake reversal. Transcripts for EAAT1, 2 and 3 were present in both rat α- and β-cells. Inhibition of EAATs by L-trans-pyrrolidine-2,4-dicarboxylate augmented intra-cellular glutamate and α-ketoglutarate contents and potentiated glucose-stimulated insulin secretion from islets and purified β-cells without affecting glucagon secretion from α-cells. In conclusion, intra-cellular glutamate-derived metabolite pools are linked to glucose-stimulated insulin but not glucagon secretion.

Keywords
  • Alanine/metabolism
  • Animals
  • Aspartic Acid/metabolism
  • Cell Membrane/metabolism/secretion
  • Cells, Cultured
  • Dicarboxylic Acids/pharmacology
  • Epinephrine/pharmacology
  • Glucagon/metabolism/secretion
  • Glucagon-Secreting Cells/metabolism/secretion
  • Glucose/metabolism/pharmacology
  • Glutamate Plasma Membrane Transport Proteins/antagonists & inhibitors/genetics/metabolism
  • Glutamic Acid/metabolism/secretion
  • Glutamine/metabolism
  • Insulin/metabolism/secretion
  • Insulin-Secreting Cells/metabolism/secretion
  • Ketoglutaric Acids/metabolism
  • Malates/metabolism
  • Male
  • Pyrrolidines/pharmacology
  • Rats
  • Rats, Wistar
  • Transcription, Genetic
  • Gamma-Aminobutyric Acid/metabolism
Citation (ISO format)
FELDMANN, Nicole et al. Reduction of plasma membrane glutamate transport potentiates insulin but not glucagon secretion in pancreatic islet cells. In: Molecular and cellular endocrinology, 2011, vol. 338, n° 1-2, p. 46–57. doi: 10.1016/j.mce.2011.02.019
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Article (Published version)
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Identifiers
ISSN of the journal0303-7207
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