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CC BY-NC-ND 4.0 · Horm Metab Res 2024; 56(03): 223-234
DOI: 10.1055/a-2236-8625
Original Article: Endocrine Research

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

Laura Wörmeyer
1   Department of General Pediatrics, Neonatology and Pediatric Cardiology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
2   Institute of Metabolic Physiology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
,
Oliver Nortmann
1   Department of General Pediatrics, Neonatology and Pediatric Cardiology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
2   Institute of Metabolic Physiology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
,
Anna Hamacher
2   Institute of Metabolic Physiology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
,
Celina Uhlemeyer
3   Institute for Vascular and Islet Cell Biology, German Diabetes Center (DDZ), Leibniz Center for Diabetes Research, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
4   German Center for Diabetes Research (DZD e.V.), Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt, Neuherberg, Germany
,
Bengt Belgardt
3   Institute for Vascular and Islet Cell Biology, German Diabetes Center (DDZ), Leibniz Center for Diabetes Research, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
4   German Center for Diabetes Research (DZD e.V.), Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt, Neuherberg, Germany
,
Daniel Eberhard
2   Institute of Metabolic Physiology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
,
Ertan Mayatepek
1   Department of General Pediatrics, Neonatology and Pediatric Cardiology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
,
Thomas Meissner
1   Department of General Pediatrics, Neonatology and Pediatric Cardiology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
,
Eckhard Lammert
2   Institute of Metabolic Physiology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
3   Institute for Vascular and Islet Cell Biology, German Diabetes Center (DDZ), Leibniz Center for Diabetes Research, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
4   German Center for Diabetes Research (DZD e.V.), Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt, Neuherberg, Germany
,
Alena Welters
1   Department of General Pediatrics, Neonatology and Pediatric Cardiology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
3   Institute for Vascular and Islet Cell Biology, German Diabetes Center (DDZ), Leibniz Center for Diabetes Research, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
› Author Affiliations Funding Information University Hospital Düsseldorf, Medical Faculty — Deutsche Forschungsgemeinschaft — http://dx.doi.org/10.13039/501100001659; 434472323 Heinrich-Heine-Universität Düsseldorf — http://dx.doi.org/10.13039/501100003484;
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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.

Key words

type 1 diabetes - islet cell protection - islet inflammation - beta cells - diabetes

Supplementary Material



Publication History

Received: 29 August 2023

Accepted after revision: 20 December 2023

Accepted Manuscript online:
02 January 2024

Article published online:
29 January 2024

© 2024. 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/).

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