A Systematic Review of the Effects of N-Methyl-D-Aspartate Receptor Antagonists on Pancreatic Islets.

IF 2.4 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Neuroendocrinology Pub Date : 2026-01-01 Epub Date: 2025-10-30 DOI:10.1159/000549276

Sabrina Wong, Gia Han Le, John Uhlig, Ellen Yang, Christine E Dri, Joshua D Rosenblat, Rodrigo B Mansur, Roger S McIntyre

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引用次数: 0

Abstract

Background: N-methyl-D-aspartate receptors (NMDARs) are widely distributed in the brain and pancreas. Preliminary evidence indicates that aberrant NMDAR-mediated glutamatergic signaling may disrupt pancreatic islet function and glucose-insulin homeostasis. The frequent comorbidity of depression and diabetes underscores the potential role of NMDAR signaling in pancreatic function as a shared pathophysiological mechanism. Herein, this systematic review aims to evaluate the effects of NMDAR antagonism on pancreatic cells (i.e., alpha, beta, delta) viability and function (i.e., activation, hormone production, and release).

Methods: We performed a systematic search on PubMed and Ovid databases from inception to September 11, 2024. A manual search was also conducted on Google Scholar and Scopus databases. Eligible studies were primary, controlled in vitro or in vivo studies investigating the effects of NMDAR antagonism on pancreatic islet function and viability. Results were synthesized and presented descriptively. Risk of bias was assessed independently by two reviewers using a modified SYRCLE risk of bias tool.

Results: We reviewed 14 studies evaluating NMDA receptor antagonism in whole islets, beta and alpha cells; however, no studies evaluated delta cells. Within beta cells, NMDAR antagonism improved glucose-stimulated insulin secretion and increased cell proliferation and viability. Similarly, alpha cells were protected against stress-induced apoptosis.

Conclusion: Our results suggest that NMDAR antagonism improves alpha and beta cell function and viability, which may have translational relevance to comorbid metabolic dysfunction in depression. These mechanisms may subserve the antidepressant effects of select NMDA antagonists (e.g., ketamine/esketamine, dextromethorphan). Further research should aim to investigate the effects of subanesthetic doses of ketamine/esketamine on pancreatic function and on delta cells.

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n -甲基- d -天冬氨酸受体拮抗剂对胰岛影响的系统综述。

n -甲基- d -天冬氨酸受体（NMDARs）广泛分布于大脑和胰腺。初步证据表明，异常的nmdar介导的谷氨酸能信号可能会破坏胰岛功能和葡萄糖-胰岛素稳态。抑郁症和糖尿病的常见合并症强调了NMDAR信号在胰腺功能中作为一种共同的病理生理机制的潜在作用。在此，本系统综述旨在评估NMDAR拮抗剂对胰腺细胞（即α、β、δ）活力和功能（即激活、激素产生和释放）的影响。方法对PubMed和Ovid数据库进行系统检索，检索时间为成立至2024年9月11日。在b谷歌Scholar和Scopus数据库中进行了人工检索。符合条件的研究是研究NMDAR拮抗剂对胰岛功能和活力影响的初步、体外或体内对照研究。对结果进行了综合和描述。偏倚风险由两位评论者使用改良的sycle偏倚风险工具独立评估。结果回顾了全胰岛、β和α细胞中NMDA受体拮抗作用的14项研究；然而，没有研究评估delta细胞。在β细胞中，NMDAR拮抗剂改善了葡萄糖刺激的胰岛素分泌，增加了细胞增殖和活力。同样，α细胞也能抵抗应激诱导的凋亡。结论NMDAR拮抗剂可改善α和β细胞的功能和活力，这可能与抑郁症共病代谢功能障碍有翻译相关性。这些机制可能支持某些NMDA拮抗剂（如氯胺酮/艾氯胺酮，右美沙芬）的抗抑郁作用。进一步的研究应旨在调查亚麻醉剂量氯胺酮/艾氯胺酮对胰腺功能和δ细胞的影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuroendocrinology 医学-内分泌学与代谢

CiteScore

8.30

自引率

2.40%

发文量

审稿时长

6-12 weeks

期刊介绍： ''Neuroendocrinology'' publishes papers reporting original research in basic and clinical neuroendocrinology. The journal explores the complex interactions between neuronal networks and endocrine glands (in some instances also immunecells) in both central and peripheral nervous systems. Original contributions cover all aspects of the field, from molecular and cellular neuroendocrinology, physiology, pharmacology, and the neuroanatomy of neuroendocrine systems to neuroendocrine correlates of behaviour, clinical neuroendocrinology and neuroendocrine cancers. Readers also benefit from reviews by noted experts, which highlight especially active areas of current research, and special focus editions of topical interest.