@article{Marquard:2015:10.1038/nm.3822,
author = {Marquard, J and Otter, S and Welters, A and Stirban, A and Fischer, A and Eglinger, J and Herebian, D and Kletke, O and Klemen, MS and Stozer, A and Wnendt, S and Piemonti, L and Kohler, M and Ferrer, J and Thorens, B and Schliess, F and Rupnik, MS and Heise, T and Berggren, P-O and Kloecker, N and Meissner, T and Mayatepek, E and Eberhard, D and Kragl, M and Lammert, E},
doi = {10.1038/nm.3822},
journal = {Nature Medicine},
pages = {363--372},
title = {Characterization of pancreatic NMDA receptors as possible drug targets for diabetes treatment},
url = {http://dx.doi.org/10.1038/nm.3822},
volume = {21},
year = {2015}
}

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TY  - JOUR
AB  - 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 Ca2+ 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.
AU  - Marquard,J
AU  - Otter,S
AU  - Welters,A
AU  - Stirban,A
AU  - Fischer,A
AU  - Eglinger,J
AU  - Herebian,D
AU  - Kletke,O
AU  - Klemen,MS
AU  - Stozer,A
AU  - Wnendt,S
AU  - Piemonti,L
AU  - Kohler,M
AU  - Ferrer,J
AU  - Thorens,B
AU  - Schliess,F
AU  - Rupnik,MS
AU  - Heise,T
AU  - Berggren,P-O
AU  - Kloecker,N
AU  - Meissner,T
AU  - Mayatepek,E
AU  - Eberhard,D
AU  - Kragl,M
AU  - Lammert,E
DO  - 10.1038/nm.3822
EP  - 372
PY  - 2015///
SN  - 1078-8956
SP  - 363
TI  - Characterization of pancreatic NMDA receptors as possible drug targets for diabetes treatment
T2  - Nature Medicine
UR  - http://dx.doi.org/10.1038/nm.3822
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000352493600018&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.nature.com/articles/nm.3822
VL  - 21
ER  - 

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