The role of N-methyl-D-aspartate receptors (NMDARs) in pancreatic islet β-cells remains poorly understood. Here, Marquard et al. report that the NMDAR antagonist MK-801 increases glucose-stimulated insulin secretion and improves glucose tolerance in mouse and human islet cells, by extending the depolarization phase in β-cells. Similar effects occurred in isolated islet cells and in mice administered another NMDAR antagonist (the cough suppressant dextromethorphan (DXM)). In diabetic db/db mice, oral DXM administration increased islet insulin content, cell mass and survival, and improved blood glucose control. In a Phase IIa trial in patients with type 2 diabetes, a single oral dose of DXM increased serum insulin concentrations and glucose tolerance.
References
Marquard, J. et al. Characterization of pancreatic NMDA receptors as possible drug targets for diabetes treatment Nature Med. 21, 363–372 (2015)
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Crunkhorn, S. Cough suppressant reverses diabetes. Nat Rev Drug Discov 14, 312 (2015). https://doi.org/10.1038/nrd4628
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DOI: https://doi.org/10.1038/nrd4628