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NMDA Receptor Antagonists Increase the Release of GLP-1 From Gut Endocrine Cells

Malgorzata Cyranka1, Thomas Monfeuga2, Natascia Vedovato1

  • 1Department of Physiology, Anatomy and Genetics, Sherrington Building, University of Oxford, Oxford, United Kingdom.

Frontiers in Pharmacology
|May 16, 2022
PubMed

Insights

N-methyl-D-aspartate (NMDA) receptor antagonists, like MK-801, increase glucagon-like peptide-1 (GLP-1) release from gut cells. Further research is crucial to understand their potential as treatments for type 2 diabetes mellitus (T2DM).

Area of Science:

  • Endocrinology and Metabolism
  • Neuropharmacology
  • Molecular Biology

Background:

  • Type 2 diabetes mellitus (T2DM) is a significant global health challenge requiring novel therapeutic strategies.
  • Existing antidiabetic drugs primarily manage hyperglycemia, but restoring pancreatic islet function is a critical unmet need.
  • N-methyl-D-aspartate (NMDA) receptor antagonists have shown potential in enhancing insulin release and beta-cell viability.

Purpose of the Study:

  • To investigate the effects of NMDA receptor antagonists on the secretion of the incretin hormone glucagon-like peptide-1 (GLP-1).
  • To explore the impact of NMDA receptor antagonists on gut hormone secretion.
  • To analyze the mRNA expression profile of glutamate-activated receptors in enteroendocrine cells.

Main Methods:

  • Utilized a murine L-cell enteroendocrine cell line (GLUTag cells) as a model system.
  • Administered the NMDA receptor antagonist MK-801 to assess its effect on GLP-1 release.
  • Performed 3' mRNA expression profiling of GLUTag cells, focusing on glutamate-activated receptors.

Main Results:

  • Demonstrated that MK-801 significantly increases GLP-1 release from GLUTag cells.
  • Provided evidence that NMDA receptor antagonists can modulate incretin hormone secretion.
  • Characterized the expression of glutamate-activated receptors within the enteroendocrine cell model.

Conclusions:

  • NMDA receptor antagonists, exemplified by MK-801, stimulate GLP-1 secretion from enteroendocrine cells.
  • The findings highlight the necessity of investigating the influence of NMDA receptor antagonists on gut hormone release.
  • Thorough evaluation of effects on gut and incretin hormones is essential before considering NMDA receptor antagonists for T2DM treatment.
Keywords:
(DMO), NMDA receptor antagonistGLUTag cellsGlucagon-like peptide 1 (GLP-1)MK-801 (dizocilpine)NMDA receptor (NMDAR)dextromethorphan

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