@article{FayyazHenkelJaptoketal.2014,
  author    = {Fayyaz, Susann and Henkel, Janin and Japtok, Lukasz and Kr{\"a}mer, Stephanie and Damm, Georg and Seehofer, Daniel and P{\"u}schel, Gerhard Paul and Kleuser, Burkhard},
  title     = {Involvement of sphingosine 1-phosphate in palmitate-induced insulin resistance of hepatocytes via the S1P(2) receptor subtype},
  series = {Diabetologia : journal of the European Association for the Study of Diabetes (EASD)},
  volume    = {57},
  journal   = {Diabetologia : journal of the European Association for the Study of Diabetes (EASD)},
  number    = {2},
  publisher = {Springer},
  address   = {New York},
  issn      = {0012-186X},
  doi       = {10.1007/s00125-013-3123-6},
  pages     = {373 -- 382},
  year      = {2014},
  abstract  = {Enhanced plasma levels of NEFA have been shown to induce hepatic insulin resistance, which contributes to the development of type 2 diabetes. Indeed, sphingolipids can be formed via a de novo pathway from the saturated fatty acid palmitate and the amino acid serine. Besides ceramides, sphingosine 1-phosphate (S1P) has been identified as a major bioactive lipid mediator. Therefore, our aim was to investigate the generation and function of S1P in hepatic insulin resistance. The incorporation of palmitate into sphingolipids was performed by rapid-resolution liquid chromatography-MS/MS in primary human and rat hepatocytes. The influence of S1P and the involvement of S1P receptors in hepatic insulin resistance was examined in human and rat hepatocytes, as well as in New Zealand obese (NZO) mice. Palmitate induced an impressive formation of extra- and intracellular S1P in rat and human hepatocytes. An elevation of hepatic S1P levels was observed in NZO mice fed a high-fat diet. Once generated, S1P was able, similarly to palmitate, to counteract insulin signalling. The inhibitory effect of S1P was abolished in the presence of the S1P(2) receptor antagonist JTE-013 both in vitro and in vivo. In agreement with this, the immunomodulator FTY720-phosphate, which binds to all S1P receptors except S1P(2), was not able to inhibit insulin signalling. These data indicate that palmitate is metabolised by hepatocytes to S1P, which acts via stimulation of the S1P(2) receptor to impair insulin signalling. In particular, S1P(2) inhibition could be considered as a novel therapeutic target for the treatment of insulin resistance.},
  language  = {en}
}
@inproceedings{HenkelCamargoSchanzeetal.2014,
  author    = {Henkel, Janine and Camargo, Rodolfo Gonzalez and Schanze, Nancy and P{\"u}schel, Gerhard Paul},
  title     = {The vicious circle of prostaglandin- and cytokine-dependent hepatic insulin resistance: a key role of prostaglandin E2},
  series = {Diabetologia : journal of the European Association for the Study of Diabetes (EASD)},
  volume    = {57},
  booktitle = {Diabetologia : journal of the European Association for the Study of Diabetes (EASD)},
  publisher = {Springer},
  address   = {New York},
  issn      = {0012-186X},
  pages     = {S241 -- S242},
  year      = {2014},
  language  = {en}
}
@article{NeuschaeferRubeLieskeKunaetal.2014,
  author    = {Neuschaefer-Rube, Frank and Lieske, Stefanie and Kuna, Manuela and Henkel, Janin and Perry, Rachel J. and Erion, Derek M. and Pesta, Dominik and Willmes, Diana M. and Brachs, Sebastian and von Loeffelholz, Christian and Tolkachov, Alexander and Schupp, Michael and Pathe-Neuschaefer-Rube, Andrea and Pfeiffer, Andreas F. H. and Shulman, Gerald I. and P{\"u}schel, Gerhard Paul and Birkenfeld, Andreas L.},
  title     = {The mammalian INDY homolog is induced by CREB in a rat model of type 2 diabetes},
  series = {Diabetes : a journal of the American Diabetes Association},
  volume    = {63},
  journal   = {Diabetes : a journal of the American Diabetes Association},
  number    = {3},
  publisher = {American Diabetes Association},
  address   = {Alexandria},
  issn      = {0012-1797},
  pages     = {1048 -- 1057},
  year      = {2014},
  language  = {en}
}