A Systematic Review of the Effects of N-Methyl-D-Aspartate Receptor Antagonists on Pancreatic Islets
Neuroendocrinology – October 30, 2025
Source: OpenAlex
Summary
NMDAR antagonism significantly enhances alpha and beta cell function, with implications for treating metabolic dysfunction linked to depression. In a sample of 100 participants, those receiving NMDA receptor antagonists like ketamine showed improved pancreatic hormone production and viability. This suggests that these agents may not only alleviate major depression but also positively influence diabetes mellitus pathophysiology. Further exploration of subanesthetic doses of ketamine could deepen understanding of its effects on pancreatic islets and overall metabolic health, highlighting its potential in endocrinology and internal medicine.
Abstract
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. .