The glial glutamate transporter 1 (GLT1) is expressed by pancreatic beta-cells and prevents glutamate-induced beta-cell death.

Détails

ID Serval
serval:BIB_1DCE840C6AA8
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
The glial glutamate transporter 1 (GLT1) is expressed by pancreatic beta-cells and prevents glutamate-induced beta-cell death.
Périodique
Journal of Biological Chemistry
Auteur(s)
Di Cairano E.S., Davalli A.M., Perego L., Sala S., Sacchi V.F., La Rosa S., Finzi G., Placidi C., Capella C., Conti P., Centonze V.E., Casiraghi F., Bertuzzi F., Folli F., Perego C.
ISSN
1083-351X (Electronic)
ISSN-L
0021-9258
Statut éditorial
Publié
Date de publication
2011
Peer-reviewed
Oui
Volume
286
Numéro
16
Pages
14007-14018
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
Glutamate is the major excitatory neurotransmitter of the central nervous system (CNS) and may induce cytotoxicity through persistent activation of glutamate receptors and oxidative stress. Its extracellular concentration is maintained at physiological concentrations by high affinity glutamate transporters of the solute carrier 1 family (SLC1). Glutamate is also present in islet of Langerhans where it is secreted by the α-cells and acts as a signaling molecule to modulate hormone secretion. Whether glutamate plays a role in islet cell viability is presently unknown. We demonstrate that chronic exposure to glutamate exerts a cytotoxic effect in clonal β-cell lines and human islet β-cells but not in α-cells. In human islets, glutamate-induced β-cell cytotoxicity was associated with increased oxidative stress and led to apoptosis and autophagy. We also provide evidence that the key regulator of extracellular islet glutamate concentration is the glial glutamate transporter 1 (GLT1). GLT1 localizes to the plasma membrane of β-cells, modulates hormone secretion, and prevents glutamate-induced cytotoxicity as shown by the fact that its down-regulation induced β-cell death, whereas GLT1 up-regulation promoted β-cell survival. In conclusion, the present study identifies GLT1 as a new player in glutamate homeostasis and signaling in the islet of Langerhans and demonstrates that β-cells critically depend on its activity to control extracellular glutamate levels and cellular integrity.
Mots-clé
Animals, Apoptosis, Autophagy, Cell Survival, Excitatory Amino Acid Transporter 2/biosynthesis, Excitatory Amino Acid Transporter 2/physiology, Gene Expression Regulation, Glutamate Plasma Membrane Transport Proteins/biosynthesis, Glutamate Plasma Membrane Transport Proteins/physiology, Glutamic Acid/chemistry, Glutamic Acid/metabolism, Homeostasis, Humans, Insulin-Secreting Cells/cytology, Islets of Langerhans/cytology, Mice, Models, Biological, Oxidative Stress
Pubmed
Web of science
Open Access
Oui
Création de la notice
06/09/2016 13:38
Dernière modification de la notice
20/08/2019 12:54
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