| Autor: |
Richard Kehm, Markus Jähnert, Stefanie Deubel, Tanina Flore, Jeannette König, Tobias Jung, Mandy Stadion, Wenke Jonas, Annette Schürmann, Tilman Grune, Annika Höhn |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
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| Zdroj: |
Redox Biology, Vol 37, Iss , Pp 101748- (2020) |
| Druh dokumentu: |
article |
| ISSN: |
2213-2317 |
| DOI: |
10.1016/j.redox.2020.101748 |
| Popis: |
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 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 diabetes-prone NZO mice. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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