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| Verfasst von: | Rhein, Sina [VerfasserIn]  |
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| | Costalunga, Riccardo [VerfasserIn] |
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| | Inderhees, Julica [VerfasserIn] |
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| | Gürtzgen, Tammo [VerfasserIn] |
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| | Faupel, Teresa Christina [VerfasserIn] |
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| | Shaheryar, Zaib [VerfasserIn] |
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| | Arrulo Pereira, Adriana [VerfasserIn] |
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| | Othman, Alaa [VerfasserIn] |
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| | Begemann, Kimberly [VerfasserIn] |
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| | Binder, Sonja [VerfasserIn] |
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| | Stölting, Ines [VerfasserIn] |
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| | Dorta, Valentina [VerfasserIn] |
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| | Nawroth, Peter Paul [VerfasserIn] |
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| | Fleming, Thomas [VerfasserIn] |
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| | Oexle, Konrad [VerfasserIn] |
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| | Prevot, Vincent [VerfasserIn] |
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| | Nogueiras, Ruben [VerfasserIn] |
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| | Meyhöfer, Svenja [VerfasserIn] |
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| | Meyhöfer, Sebastian M. [VerfasserIn] |
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| | Schwaninger, Markus [VerfasserIn] |
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| Titel: | The reactive pyruvate metabolite dimethylglyoxal mediates neurological consequences of diabetes |
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| Verf.angabe: | Sina Rhein, Riccardo Costalunga, Julica Inderhees, Tammo Gürtzgen, Teresa Christina Faupel, Zaib Shaheryar, Adriana Arrulo Pereira, Alaa Othman, Kimberly Begemann, Sonja Binder, Ines Stölting, Valentina Dorta, Peter P. Nawroth, Thomas Fleming, Konrad Oexle, Vincent Prevot, Ruben Nogueiras, Svenja Meyhöfer, Sebastian M. Meyhöfer & Markus Schwaninger |
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| E-Jahr: | 2024 |
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| Jahr: | 10 July 2024 |
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| Umfang: | 20 S. |
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| Illustrationen: | Illustrationen |
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| Fussnoten: | Gesehen am 07.03.2025 |
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| Titel Quelle: | Enthalten in: Nature Communications |
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| Ort Quelle: | [London] : Springer Nature, 2010 |
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| Jahr Quelle: | 2024 |
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| Band/Heft Quelle: | 15(2024), Artikel-ID 5745, Seite 1-20 |
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| ISSN Quelle: | 2041-1723 |
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| Abstract: | Complications of diabetes are often attributed to glucose and reactive dicarbonyl metabolites derived from glycolysis or gluconeogenesis, such as methylglyoxal. However, in the CNS, neurons and endothelial cells use lactate as energy source in addition to glucose, which does not lead to the formation of methylglyoxal and has previously been considered a safer route of energy consumption than glycolysis. Nevertheless, neurons and endothelial cells are hotspots for the cellular pathology underlying neurological complications in diabetes, suggesting a cause that is distinct from other diabetes complications and independent of methylglyoxal. Here, we show that in clinical and experimental diabetes plasma concentrations of dimethylglyoxal are increased. In a mouse model of diabetes, ilvb acetolactate-synthase-like (ILVBL, HACL2) is the enzyme involved in formation of increased amounts of dimethylglyoxal from lactate-derived pyruvate. Dimethylglyoxal reacts with lysine residues, forms Nε−3-hydroxy-2-butanonelysine (HBL) as an adduct, induces oxidative stress more strongly than other dicarbonyls, causes blood-brain barrier disruption, and can mimic mild cognitive impairment in experimental diabetes. These data suggest dimethylglyoxal formation as a pathway leading to neurological complications in diabetes that is distinct from other complications. Importantly, dimethylglyoxal formation can be reduced using genetic, pharmacological and dietary interventions, offering new strategies for preventing CNS dysfunction in diabetes. |
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| DOI: | doi:10.1038/s41467-024-50089-3 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
kostenfrei: Volltext: https://doi.org/10.1038/s41467-024-50089-3 |
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| | kostenfrei: Volltext: https://www.nature.com/articles/s41467-024-50089-3 |
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| | DOI: https://doi.org/10.1038/s41467-024-50089-3 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | Blood-brain barrier |
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| | Cerebrovascular disorders |
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| | Diabetes complications |
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| | Dietary carbohydrates |
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| | Molecular medicine |
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| K10plus-PPN: | 1919316280 |
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| Verknüpfungen: | → Zeitschrift |
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¬The¬ reactive pyruvate metabolite dimethylglyoxal mediates neurological consequences of diabetes / Rhein, Sina [VerfasserIn]; 10 July 2024 (Online-Ressource)
