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Need for Better Diabetes Treatment: The Therapeutic Potential of NMDA Receptor Antagonists

A Welters1, E Lammert1, E Mayatepek1

  • 1Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital Düsseldorf, Germany.

Klinische Padiatrie
|December 16, 2016
PubMed

Insights

Inhibiting N-methyl-D-aspartate receptors (NMDARs) in the pancreas boosts insulin secretion and improves glucose tolerance in diabetes. This suggests NMDAR antagonists may offer new protective treatments for diabetes mellitus.

Area of Science:

  • Endocrinology and Metabolism
  • Neuroscience
  • Pharmacology

Background:

  • Diabetes mellitus is a prevalent metabolic disorder requiring optimal blood glucose control to prevent complications.
  • Current diabetes treatments, while improved, do not offer a cure for type 1 or type 2 diabetes.
  • Research focuses on developing beta-cell protective agents to prevent or reverse diabetes onset.

Purpose of the Study:

  • To investigate the role of pancreatic N-methyl-D-aspartate receptors (NMDARs) in glucose homeostasis and beta-cell function.
  • To explore the therapeutic potential of NMDAR inhibition as an adjunct treatment for diabetes mellitus.

Main Methods:

  • Utilized genetic and pharmacological inhibition of pancreatic NMDARs in mouse models.
  • Administered dextromethorphan, an NMDAR antagonist, to mice and individuals with diabetes.
  • Assessed glucose-stimulated insulin secretion, glucose tolerance, and islet cell survival under diabetogenic conditions.

Main Results:

  • Inhibition of pancreatic NMDARs significantly increased glucose-stimulated insulin secretion in mouse and human islets.
  • Pharmacological NMDAR inhibition with dextromethorphan improved glucose tolerance in diabetic mice and individuals.
  • NMDAR antagonists promoted islet cell survival under conditions that typically induce diabetes.

Conclusions:

  • Pancreatic NMDARs play a crucial role in regulating insulin secretion and glucose metabolism.
  • NMDAR antagonists, such as dextromethorphan, show promise as a novel adjunct therapy for diabetes mellitus.
  • Targeting NMDARs offers a potential strategy for developing beta-cell protective and glucose-lowering medications.

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