ArticleScientific reports2017
An excessive increase in glutamate contributes to glucose-toxicity in β-cells via activation of pancreatic NMDA receptors in rodent diabetes.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
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Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 92 citations in OpenAlex.
- A Systematic Review of the Effects of N-Methyl-D-Aspartate Receptor Antagonists on Pancreatic Islets.Neuroendocrinology · 2026Pooled it
- Transcriptomic signatures of treatment response to the combination of escitalopram and memantine or placebo in late-life depression.Molecular psychiatry · 2021Trial
- Deep single-cell decoding of human pancreatic islets reveals T2D β-cell gene expression defects.The EMBO journal · 2026Article
- Combined purslane ethanolic extract and metformin attenuate cognitive dysfunction in HFD/STZ-induced diabetic rats via modulation of oxidative stress, neuroinflammation, and neurotransmitters.BMC pharmacology & toxicology · 2026Article
- Polycaprolactone scaffolds promote a regeneration-supportive metabolic response attenuated in diabetes.Regenerative biomaterials · 2026Article
- Integrated Genomic-Metabolomic Analysis for Tri-Categorical Classification of Type 2 Diabetes Status in the Korean Ansan-Ansung Cohort.International journal of molecular sciences · 2025Article
- Neurotransmitter Alterations in Prediabetes and Type 2 Diabetes Mellitus: A Narrative Review.International journal of molecular sciences · 2025Review
- Loss of CD98HC phosphorylation by ATM impairs antiporter trafficking and drives glutamate toxicity in Ataxia telangiectasia.Nature communications · 2025Article
- Memantine abrogates testicular dysfunction induced by risperidone in rats with a potential role of ERK1/2-Nrf2-caspase-3 signaling pathway.Scientific reports · 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
- Blood metabolomic profile in patients with type 2 diabetes mellitus with diabetic peripheral neuropathic pain.Journal of diabetes investigation · 2025Article
- Early Postpartum Metabolic Heterogeneity Among Women Who Progressed to Type 2 Diabetes After Gestational Diabetes: A Prospective Cohort.Diabetes/metabolism research and reviews · 2025Article
- Metabolomics uncovers the diabetes metabolic network: from pathophysiological mechanisms to clinical applications.Frontiers in endocrinology · 2025Review
- Inhibition of mTOR prevents glucotoxicity-mediated increase of SA-beta-gal, p16Biogerontology · 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
- Endoplasmic reticulum stress and therapeutic strategies in metabolic, neurodegenerative diseases and cancer.Molecular medicine (Cambridge, Mass.) · 2024Review
- 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
- Alterations of the glutamatergic system in diabetes mellitus.Metabolic brain disease · 2024Review
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In the nervous system, excessive activation of NMDA receptors causes neuronal injury. Although activation of NMDARs has been proposed to contribute to the progress of diabetes, little is known about the effect of excessive long-term activation of NMDARs on β-cells, especially under the challenge of hyperglycemia. Here we thoroughly investigated whether endogenous glutamate aggravated β-cell dysfunction under chronic exposure to high-glucose via activation of NMDARs. The glutamate level was increased in plasma of diabetic mice or patients and in the supernatant of β-cell lines after treatment with high-glucose for 72 h. Decomposing the released glutamate improved GSIS of β-cells under chronic high-glucose exposure. Long-term treatment of β-cells with NMDA inhibited cell viability and decreased GSIS. These effects were eliminated by GluN1 knockout. The NMDAR antagonist MK-801 or GluN1 knockout prevented high-glucose-induced dysfunction in β-cells. MK-801 also decreased the expression of pro-inflammatory cytokines, and inhibited I-κB degradation, ROS generation and NLRP3 inflammasome expression in β-cells exposed to high-glucose. Furthermore, another NMDAR antagonist, Memantine, improved β-cells function in diabetic mice. Taken together, these findings indicate that an increase of glutamate may contribute to the development of diabetes through excessive activation of NMDARs in β-cells, accelerating β-cells dysfunction and apoptosis induced by hyperglycemia.
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