Richard Kehm, Markus Jähnert, Stefanie Deubel, Tanina Flore, Jeannette König, Tobias Jung, Mandy Stadion, Wenke Jonas, Annette Schürmann, Tilman Grune, Annika Höhn
- Overnutrition contributes to insulin resistance, obesity and metabolic stress, initiating a loss of functional beta-cells and diabetes development. Whether these damaging effects are amplified in advanced age is barely investigated. Therefore, New Zealand Obese (NZO) mice, a well-established model for the investigation of human obesity-associated type 2 diabetes, were fed a metabolically challenging diet with a high-fat, carbohydrate restricted period followed by a carbohydrate intervention in young as well as advanced age. Interestingly, while young NZO mice developed massive hyperglycemia in response to carbohydrate feeding, leading to beta-cell dysfunction and cell death, aged counterparts compensated the increased insulin demand by persistent beta-cell function and beta-cell mass expansion. Beta-cell loss in young NZO islets was linked to increased expression of thioredoxin-interacting protein (TXNIP), presumably initiating an apoptosis-signaling cascade via caspase-3 activation. In contrast, islets of aged NZOs exhibited aOvernutrition contributes to insulin resistance, obesity and metabolic stress, initiating a loss of functional beta-cells and diabetes development. Whether these damaging effects are amplified in advanced age is barely investigated. Therefore, New Zealand Obese (NZO) mice, a well-established model for the investigation of human obesity-associated type 2 diabetes, were fed a metabolically challenging diet with a high-fat, carbohydrate restricted period followed by a carbohydrate intervention in young as well as advanced age. Interestingly, while young NZO mice developed massive hyperglycemia in response to carbohydrate feeding, leading to beta-cell dysfunction and cell death, aged counterparts compensated the increased insulin demand by persistent beta-cell function and beta-cell mass expansion. Beta-cell loss in young NZO islets was linked to increased expression of thioredoxin-interacting protein (TXNIP), presumably initiating an apoptosis-signaling cascade via caspase-3 activation. In contrast, islets of aged NZOs exhibited a sustained redox balance without changes in TXNIP expression, associated with higher proliferative potential by cell cycle activation. These findings support the relevance of a maintained proliferative potential and redox homeostasis for preserving islet functionality under metabolic stress, with the peculiarity that this adaptive response emerged with advanced age in diabetesprone NZO mice.…
MetadatenVerfasserangaben: | Richard KehmORCiDGND, Markus JähnertORCiD, Stefanie Deubel, Tanina Flore, Jeannette KönigORCiDGND, Tobias JungORCiDGND, Mandy StadionORCiDGND, Wenke JonasORCiDGND, Annette SchürmannORCiDGND, Tilman GruneORCiDGND, Annika HöhnORCiDGND |
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DOI: | https://doi.org/10.1016/j.redox.2020.101748 |
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ISSN: | 2213-2317 |
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Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/33128997 |
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Titel des übergeordneten Werks (Englisch): | Redox Biology |
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Verlag: | Elsevier |
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Verlagsort: | Amsterdam |
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Publikationstyp: | Wissenschaftlicher Artikel |
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Sprache: | Englisch |
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Datum der Erstveröffentlichung: | 07.10.2020 |
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Erscheinungsjahr: | 2020 |
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Datum der Freischaltung: | 08.11.2023 |
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Freies Schlagwort / Tag: | aging; beta-cells; cell cycle; metabolic stress; redox homeostasis; thioredoxin-interacting protein |
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Band: | 37 |
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Aufsatznummer: | 101748 |
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Seitenanzahl: | 11 |
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Fördernde Institution: | German Ministry of Education and Research (BMBF)Federal Ministry of; Education & Research (BMBF); State of Brandenburg (DZD) [82DZD00302] |
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Organisationseinheiten: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Ernährungswissenschaft |
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DDC-Klassifikation: | 5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften |
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Peer Review: | Referiert |
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Publikationsweg: | Open Access / Gold Open-Access |
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| DOAJ gelistet |
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Lizenz (Deutsch): | CC-BY-NC-ND - Namensnennung, nicht kommerziell, keine Bearbeitungen 4.0 International |
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