@article{KehmRueckriemenWeberetal.2019,
  author    = {Kehm, Richard and R{\"u}ckriemen, Jana and Weber, Daniela and Deubel, Stefanie and Grune, Tilman and H{\"o}hn, Annika},
  title     = {Endogenous advanced glycation end products in pancreatic islets after short-term carbohydrate intervention in obese, diabetes-prone mice},
  series = {Nutrition \& Diabetes},
  volume    = {9},
  journal   = {Nutrition \& Diabetes},
  publisher = {Nature Publ. Group},
  address   = {London},
  issn      = {2044-4052},
  doi       = {10.1038/s41387-019-0077-x},
  pages     = {5},
  year      = {2019},
  abstract  = {Diet-induced hyperglycemia is described as one major contributor to the formation of advanced glycation end products (AGEs) under inflammatory conditions, crucial in type 2 diabetes progression. Previous studies have indicated high postprandial plasma AGE-levels in diabetic patients and after long-term carbohydrate feeding in animal models. Pancreatic islets play a key role in glucose metabolism; thus, their susceptibility to glycation reactions due to high amounts of dietary carbohydrates is of special interest. Therefore, diabetes-prone New Zealand Obese (NZO) mice received either a carbohydrate-free, high-fat diet (CFD) for 11 weeks or were additionally fed with a carbohydrate-rich diet (CRD) for 7 days. In the CRD group, hyperglycemia and hyperinsulinemia were induced accompanied by increasing plasma 3-nitrotyrosine (3-NT) levels, higher amounts of 3-NT and inducible nitric oxide synthase (iNOS) within pancreatic islets. Furthermore, N-epsilon-carboxymethyllysine (CML) was increased in the plasma of CRD-fed NZO mice and substantially higher amounts of arg-pyrimidine, pentosidine and the receptor for advanced glycation end products (RAGE) were observed in pancreatic islets. These findings indicate that a short-term intervention with carbohydrates is sufficient to form endogenous AGEs in plasma and pancreatic islets of NZO mice under hyperglycemic and inflammatory conditions.},
  language  = {en}
}
@article{KehmJaehnertDeubeletal.2020,
  author    = {Kehm, Richard and J{\"a}hnert, Markus and Deubel, Stefanie and Flore, Tanina and K{\"o}nig, Jeannette and Jung, Tobias and Stadion, Mandy and Jonas, Wenke and Sch{\"u}rmann, Annette and Grune, Tilman and H{\"o}hn, Annika},
  title     = {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)},
  series = {Redox Biology},
  volume    = {37},
  journal   = {Redox Biology},
  publisher = {Elsevier},
  address   = {Amsterdam},
  issn      = {2213-2317},
  doi       = {10.1016/j.redox.2020.101748},
  pages     = {11},
  year      = {2020},
  abstract  = {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.},
  language  = {en}
}