ArticleNature medicine2015
Characterization of pancreatic NMDA receptors as possible drug targets for diabetes treatment.
Article in Nature medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 2 of them syntheses that pooled it.
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Who cites it
86 citing papers in PubMed, 2 syntheses or guidelines pooled it, 161 citations in OpenAlex.
- A Systematic Review of the Effects of N-Methyl-D-Aspartate Receptor Antagonists on Pancreatic Islets.Neuroendocrinology · 2026Pooled it
- The effect of glycine administration on the characteristics of physiological systems in human adults: A systematic review.GeroScience · 2024Pooled it
- Effects of dextromethorphan as add-on to sitagliptin on blood glucose and serum insulin concentrations in individuals with type 2 diabetes mellitus: a randomized, placebo-controlled, double-blinded, multiple crossover, single-dose clinical trial.Diabetes, obesity & metabolism · 2016Trial
- Metabolic Stress Shifts the Function of KArchiv der Pharmazie · 2026Article
- CHAC1-linked NRF2 protein expression participates in pancreatic islet protection by dextrorphan.iScience · 2026Article
- Deep single-cell decoding of human pancreatic islets reveals T2D β-cell gene expression defects.The EMBO journal · 2026Article
- Glycine-GLRA1-calmodulin signaling regulates endoplasmic reticulum calcium to sustain insulin secretion and β-cell function.Life metabolism · 2026Article
- Activation of the Pancreatic "Metabolic Synapse" Aggravates Type 2 Diabetes Mellitus by Inducing PANoptosis in β-Cells.Diabetes · 2026Article
- Association BetweenBrain sciences · 2026Article
- Mammalian Tolerance to Amino Acid Heterochirality.Chembiochem : a European journal of chemical biology · 2025Review
- Molecular correlates of glycine receptor activity in human β cells.Molecular metabolism · 2025Article
- Disease-modifying pharmacological treatments of type 1 diabetes: Molecular mechanisms, target checkpoints, and possible combinatorial treatments.Pharmacological reviews · 2025Review
- Parkinson's disease and glucose metabolism impairment.Translational neurodegeneration · 2025Review
- Single-cell decoding of human islet cell type-specific alterations in type 2 diabetes reveals converging genetic- and state-drivenbioRxiv : the preprint server for biology · 2025Article
- Mechanisms of NMDA Receptor Inhibition by Biguanide Compounds.Pharmaceuticals (Basel, Switzerland) · 2024Article
- NMDA Suppresses Pancreatic ABCA1 Expression through the MEK/ERK/LXR Pathway in Pancreatic Beta Cells.Nutrients · 2024Article
- Hyperglycemia impairs EAAT2 glutamate transporter trafficking and glutamate clearance in islets of Langerhans: implications for type 2 diabetes pathogenesis and treatment.American journal of physiology. Endocrinology and metabolism · 2024Article
- Involvement of γ-Aminobutyric Acid and N-methyl-D-aspartate Receptors in Diabetic Gastropathy in Rats: Possible Beneficial Effect of Prolonged Treatment with Insulin and Magnesium Supplement.Archives of Razi Institute · 2024Article
- Article
- The N-Methyl-D-Aspartate Receptor Antagonist Dextromethorphan Improves Glucose Homeostasis and Preserves Pancreatic Islets in NOD Mice.Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme · 2024Article
26 more citing papers are in PubMed but not listed here.
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Authors and funding
25 authors at 10 institutions in 7 countries.
Funding
Abstract
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.