Journal article
Interaction between magnesium and methylglyoxal in diabetic polyneuropathy and neuronal models
Molecular metabolism (Germany), Vol.43, pp.101114-101114
01/01/2021
DOI: 10.1016/j.molmet.2020.101114
PMCID: PMC7704399
PMID: 33166742
Abstract
Objective: The lack of effective treatments against diabetic sensorimotor polyneuropathy demands the search for new strategies to combat or prevent the condition. Because reduced magnesium and increased methylglyoxal levels have been implicated in the development of both type 2 diabetes and neuropathic pain, we aimed to assess the putative interplay of both molecules with diabetic sensorimotor polyneuropathy.
Methods: In a cross-sectional study, serum magnesium and plasma methylglyoxal levels were measured in recently diagnosed type 2 diabetes patients with (n = 51) and without (n = 184) diabetic sensorimotor polyneuropathy from the German Diabetes Study baseline cohort. Peripheral nerve function was assessed using nerve conduction velocity and quantitative sensory testing. Human neuroblastoma cells (SH-SY5Y) and mouse dorsal root ganglia cells were used to characterize the neurotoxic effect of methylglyoxal and/or neuroprotective effect of magnesium.
Results: Here, we demonstrate that serum magnesium concentration was reduced in recently diagnosed type 2 diabetes patients with diabetic sensorimotor polyneuropathy and inversely associated with plasma methylglyoxal concentration. Magnesium, methylglyoxal, and, importantly, their interaction were strongly interrelated with methylglyoxal-dependent nerve dysfunction and were predictive of changes in nerve function. Magnesium supplementation prevented methylglyoxal neurotoxicity in differentiated SH-SY5Y neuron-like cells due to reduction of intracellular methylglyoxal formation, while supplementation with the divalent cations zinc and manganese had no effect on methylglyoxal neurotoxicity. Furthermore, the downregulation of mitochondrial activity in mouse dorsal root ganglia cells and consequently the enrichment of triosephosphates, the primary source of methylglyoxal, resulted in neurite degeneration, which was completely prevented through magnesium supplementation.
Conclusions: These multifaceted findings reveal a novel putative pathophysiological pathway of hypomagnesemia-induced carbonyl stress leading to neuronal damage and merit further investigations not only for diabetic sensorimotor polyneuropathy but also other neurodegenerative diseases associated with magnesium deficiency and impaired energy metabolism. (C) 2020 The Authors. Published by Elsevier GmbH.
Details
- Title: Subtitle
- Interaction between magnesium and methylglyoxal in diabetic polyneuropathy and neuronal models
- Creators
- Alexander Strom - Deutsches Diabetes-Zentrum e.V.Klaus Strassburger - Deutsches Diabetes-Zentrum e.V.Martin Schmuck - Leibniz Institute of Environmental MedicineHanna Shevalye - University of IowaEric Davidson - University of IowaFariba Zivehe - Deutsches Diabetes-Zentrum e.V.Gidon Boenhof - Heinrich Heine Univ, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Clin Diabetol, Dusseldorf, GermanyRudolph Reimer - Leibniz Institute of Virology (LIV)Bengt-Frederik Belgardt - German Center for Diabetes ResearchThomas Fleming - University Hospital HeidelbergBarbara Biermann - Sensory (United States)Volker Burkart - Deutsches Diabetes-Zentrum e.V.Karsten Muessig - Heinrich Heine Univ, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Clin Diabetol, Dusseldorf, GermanyJulia Szendroedi - Heinrich Heine University DüsseldorfMark A. Yorek - Iowa City VA Health Care SystemEllen Fritsche - Leibniz Institute of Environmental MedicinePeter P. Nawroth - German Center for Diabetes ResearchMichael Roden - Heinrich Heine University DüsseldorfDan Ziegler - Deutsches Diabetes-Zentrum e.V.GDS Group
- Resource Type
- Journal article
- Publication Details
- Molecular metabolism (Germany), Vol.43, pp.101114-101114
- DOI
- 10.1016/j.molmet.2020.101114
- PMID
- 33166742
- PMCID
- PMC7704399
- NLM abbreviation
- Mol Metab
- ISSN
- 2212-8778
- eISSN
- 2212-8778
- Publisher
- Elsevier
- Number of pages
- 10
- Grant note
- Federal Ministry for Research (BMBF); Federal Ministry of Education & Research (BMBF) German Diabetes Association award Ministry of Culture and Science of the State of North Rhine Westphalia (MKW NRW) German Federal Ministry of Health (BMG) FKZ82DZD00202 / German Center for Diabetes Research (DZD) DK107339-04 / National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) German Diabetes Center Training and Feasibility Grant; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 01/01/2021
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine; Ophthalmology and Visual Sciences
- Record Identifier
- 9984360156602771
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