TY  - JOUR
A1  - Kehm, Richard
A1  - Jähnert, Markus
A1  - Deubel, Stefanie
A1  - Flore, Tanina
A1  - König, Jeannette
A1  - Jung, Tobias
A1  - Stadion, Mandy
A1  - Jonas, Wenke
A1  - Schürmann, Annette
A1  - Grune, Tilman
A1  - Höhn, Annika
T1  - Redox homeostasis and cell cycle activation mediate beta-cell mass expansion in aged, diabetes-prone mice under metabolic stress conditions: role of thioredoxin-interacting protein (TXNIP)
JF  - Redox Biology
N2  - 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 diabetesprone NZO mice.
KW  - aging
KW  - redox homeostasis
KW  - metabolic stress
KW  - beta-cells
KW  - cell cycle
KW  - thioredoxin-interacting protein
Y1  - 2020
U6  - https://doi.org/10.1016/j.redox.2020.101748
SN  - 2213-2317
VL  - 37
PB  - Elsevier
CY  - Amsterdam
ER  -