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

Authors :
Wörmeyer L
Nortmann O
Hamacher A
Uhlemeyer C
Belgardt B
Eberhard D
Mayatepek E
Meissner T
Lammert E
Welters A
Source :
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme [Horm Metab Res] 2024 Mar; Vol. 56 (3), pp. 223-234. Date of Electronic Publication: 2024 Jan 02.
Publication Year :
2024

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.<br />Competing Interests: A.W., T.M., E.M. and E.L. declare the following competing financial interests: these authors are inventors of the US patent 10,464,904 entitled “Dextrorphan-derivatives with suppressed central nervous activity”; and T.M. and E.L. are inventors of the US patent 9,370,511 entitled “Morphinan-derivatives for treating diabetes and related disorders.”<br /> (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Details

Language :
English
ISSN :
1439-4286
Volume :
56
Issue :
3
Database :
MEDLINE
Journal :
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme
Publication Type :
Academic Journal
Accession number :
38168730
Full Text :
https://doi.org/10.1055/a-2236-8625