The N-Methyl-D-Aspartate Receptor Antagonist Dextromethorphan Improves Glucose Homeostasis and Preserves Pancreatic Islets in NOD Mice

Horm Metab Res. 2024 Mar;56(3):223-234. doi: 10.1055/a-2236-8625. Epub 2024 Jan 2.

Abstract

For treatment of type 1 diabetes mellitus, a combination of immune-based interventions and medication to promote beta-cell survival and proliferation has been proposed. Dextromethorphan (DXM) is an N-methyl-D-aspartate receptor antagonist with a good safety profile, and to date, preclinical and clinical evidence for blood glucose-lowering and islet-cell-protective effects of DXM have only been provided for animals and individuals with type 2 diabetes mellitus. Here, we assessed the potential anti-diabetic effects of DXM in the non-obese diabetic mouse model of type 1 diabetes. More specifically, we showed that DXM treatment led to five-fold higher numbers of pancreatic islets and more than two-fold larger alpha- and beta-cell areas compared to untreated mice. Further, DXM treatment improved glucose homeostasis and reduced diabetes incidence by 50%. Our data highlight DXM as a novel candidate for adjunct treatment of preclinical or recent-onset type 1 diabetes.

MeSH terms

  • Animals
  • Blood Glucose
  • Dextromethorphan / pharmacology
  • Dextromethorphan / therapeutic use
  • Diabetes Mellitus, Type 1* / drug therapy
  • Diabetes Mellitus, Type 2*
  • Homeostasis
  • Insulin
  • Islets of Langerhans*
  • Mice
  • Mice, Inbred NOD
  • Receptors, N-Methyl-D-Aspartate / therapeutic use

Substances

  • Dextromethorphan
  • Receptors, N-Methyl-D-Aspartate
  • Insulin
  • Blood Glucose