Characterization of pancreatic NMDA receptors as possible drug targets for diabetes treatment.

Détails

ID Serval
serval:BIB_76486F09E4DC
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Characterization of pancreatic NMDA receptors as possible drug targets for diabetes treatment.
Périodique
Nature Medicine
Auteur(s)
Marquard J., Otter S., Welters A., Stirban A., Fischer A., Eglinger J., Herebian D., Kletke O., Klemen M.S., Stožer A., Wnendt S., Piemonti L., Köhler M., Ferrer J., Thorens B., Schliess F., Rupnik M.S., Heise T., Berggren P.O., Klöcker N., Meissner T., Mayatepek E., Eberhard D., Kragl M., Lammert E.
ISSN
1546-170X (Electronic)
ISSN-L
1078-8956
Statut éditorial
Publié
Date de publication
2015
Volume
21
Numéro
4
Pages
363-372
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
In the nervous system, NMDA receptors (NMDARs) participate in neurotransmission and modulate the viability of neurons. In contrast, little is known about the role of NMDARs in pancreatic islets and the insulin-secreting beta cells whose functional impairment contributes to diabetes mellitus. Here we found that inhibition of NMDARs in mouse and human islets enhanced their glucose-stimulated insulin secretion (GSIS) and survival of islet cells. Further, NMDAR inhibition prolonged the amount of time that glucose-stimulated beta cells spent in a depolarized state with high cytosolic Ca(2+) concentrations. We also noticed that, in vivo, the NMDAR antagonist dextromethorphan (DXM) enhanced glucose tolerance in mice, and that in vitro dextrorphan, the main metabolite of DXM, amplified the stimulatory effect of exendin-4 on GSIS. In a mouse model of type 2 diabetes mellitus (T2DM), long-term treatment with DXM improved islet insulin content, islet cell mass and blood glucose control. Further, in a small clinical trial we found that individuals with T2DM treated with DXM showed enhanced serum insulin concentrations and glucose tolerance. Our data highlight the possibility that antagonists of NMDARs may provide a useful adjunct treatment for diabetes.
Pubmed
Web of science
Création de la notice
24/04/2015 7:06
Dernière modification de la notice
20/08/2019 14:33
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