@article{JaptokSchmitzFayyazetal.2015,
  author    = {Japtok, Lukasz and Schmitz, Elisabeth I. and Fayyaz, Susann and Kr{\"a}mer, Stephanie and Hsu, Leigh J. and Kleuser, Burkhard},
  title     = {Sphingosine 1-phosphate counteracts insulin signaling in pancreatic beta-cells via the sphingosine 1-phosphate receptor subtype 2},
  series = {The FASEB journal : the official journal of the Federation of American Societies for Experimental Biology},
  volume    = {29},
  journal   = {The FASEB journal : the official journal of the Federation of American Societies for Experimental Biology},
  number    = {8},
  publisher = {Federation of American Societies for Experimental Biology},
  address   = {Bethesda},
  issn      = {0892-6638},
  doi       = {10.1096/fj.14-263194},
  pages     = {3357 -- 3369},
  year      = {2015},
  abstract  = {Glucolipotoxic stress has been identified as a key player in the progression of pancreatic beta-cell dysfunction contributing to insulin resistance and the development of type 2 diabetes mellitus (T2D). It has been suggested that bioactive lipid intermediates, formed under lipotoxic conditions, are involved in these processes. Here, we show that sphingosine 1-phosphate (S1P) levels are not only increased in palmitate-stimulated pancreatic beta-cells but also regulate beta-cell homeostasis in a divergent manner. Although S1P possesses a prosurvival effect in beta-cells, an enhanced level of the sphingolipid antagonizes insulin-mediated cell growth and survival via the sphingosine 1-phosphate receptor subtype 2 (S1P(2)) followed by an inhibition of Akt-signaling. In an attempt to investigate the role of the S1P/S1P(2) axis in vivo, the New Zealand obese (NZO) diabetic mouse model, characterized by beta-cell loss under high-fat diet (HFD) conditions, was used. The occurrence of T2D was accompanied by an increase of plasma S1P levels. To examine whether S1P contributes to the morphologic changes of islets via S1P(2), the receptor antagonist JTE-013 was administered. Most interestingly, JTE-013 rescued beta-cell damage clearly indicating an important role of the S1P(2) in beta-cell homeostasis. Therefore, the present study provides a new therapeutic strategy to diminish beta-cell dysfunction and the development of T2D.},
  language  = {en}
}
@article{JonasKluthHelmsetal.2022,
  author    = {Jonas, Wenke and Kluth, Oliver and Helms, Anett and Voss, Sarah and Jahnert, Markus and Gottmann, Pascal and Speckmann, Thilo and Knebel, Birgit and Chadt, Alexandra and Al-Hasani, Hadi and Sch{\"u}rmann, Annette and Vogel, Heike},
  title     = {Identification of novel genes involved in hyperglycemia in mice},
  series = {International journal of molecular sciences},
  volume    = {23},
  journal   = {International journal of molecular sciences},
  number    = {6},
  publisher = {MDPI},
  address   = {Basel},
  issn      = {1661-6596},
  doi       = {10.3390/ijms23063205},
  pages     = {13},
  year      = {2022},
  abstract  = {Current attempts to prevent and manage type 2 diabetes have been moderately effective, and a better understanding of the molecular roots of this complex disease is important to develop more successful and precise treatment options. Recently, we initiated the collective diabetes cross, where four mouse inbred strains differing in their diabetes susceptibility were crossed with the obese and diabetes-prone NZO strain and identified the quantitative trait loci (QTL) Nidd13/NZO, a genomic region on chromosome 13 that correlates with hyperglycemia in NZO allele carriers compared to B6 controls. Subsequent analysis of the critical region, harboring 644 genes, included expression studies in pancreatic islets of congenic Nidd13/NZO mice, integration of single-cell data from parental NZO and B6 islets as well as haplotype analysis. Finally, of the five genes (Acot12, S100z, Ankrd55, Rnf180, and Iqgap2) within the polymorphic haplotype block that are differently expressed in islets of B6 compared to NZO mice, we identified the calcium-binding protein S100z gene to affect islet cell proliferation as well as apoptosis when overexpressed in MINE cells. In summary, we define S100z as the most striking gene to be causal for the diabetes QTL Nidd13/NZO by affecting beta-cell proliferation and apoptosis. Thus, S100z is an entirely novel diabetes gene regulating islet cell function.},
  language  = {en}
}