@article{SalkerSinghZengetal.2017,
  author    = {Salker, Madhuri S. and Singh, Yogesh and Zeng, Ni and Chen, Hong and Zhang, Shaqiu and Umbach, Anja T. and Fakhri, Hajar and Kohlhofer, Ursula and Quintanilla-Martinez, Leticia and Durairaj, Ruban R. Peter and Barros, Flavio S. V. and Vrljicak, Pavle and Ott, Sascha and Brucker, Sara Y. and Wallwiener, Diethelm and Madunić, Ivana Vrhovac and Breljak, Davorka and Sabolić, Ivan and Koepsell, Hermann and Brosens, Jan J. and Lang, Florian},
  title     = {Loss of endometrial sodium glucose cotransporter SGLT1 is detrimental to embryo survival and fetal growth in pregnancy},
  series = {Scientific Reports},
  volume    = {7},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-017-11674-3},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173814},
  year      = {2017},
  abstract  = {Embryo implantation requires a hospitable uterine environment. A key metabolic change that occurs during the peri-implantation period, and throughout early pregnancy, is the rise in endometrial glycogen content. Glycogen accumulation requires prior cellular uptake of glucose. Here we show that both human and murine endometrial epithelial cells express the high affinity Na\(^+\)-coupled glucose carrier SGLT1. Ussing chamber experiments revealed electrogenic glucose transport across the endometrium in wild type (\(Slc5a1^{+/+}\)) but not in SGLT1 defcient (\(Slc5a1^{-/-}\)) mice. Endometrial glycogen content, litter size and weight of offspring at birth were signifcantly lower in \(Slc5a1^{-/-}\) mice. In humans, \(SLC5A1\) expression was upregulated upon decidualization of primary endometrial stromal cells. Endometrial \(SLC5A1\) expression during the implantation window was attenuated in patients with recurrent pregnancy loss when compared with control subjects. Our fndings reveal a novel mechanism establishing adequate endometrial glycogen stores for pregnancy. Disruption of this histiotrophic pathway leads to adverse pregnancy outcome.},
  language  = {en}
}
@article{BhavsarSinghSharmaetal.2016,
  author    = {Bhavsar, Shefalee K. and Singh, Yogesh and Sharma, Piyush and Khairnar, Vishal and Hosseinzadeh, Zohreh and Zhang, Shaqiu and Palmada, Monica and Sabolic, Ivan and Koepsell, Hermann and Lang, Karl S. and Lang, Philipp A. and Lang, Florian},
  title     = {Expression of JAK3 Sensitive Na\(^+\) Coupled Glucose Carrier SGLT1 in Activated Cytotoxic T Lymphocytes},
  series = {Cellular Physiology and Biochemistry},
  volume    = {39},
  journal   = {Cellular Physiology and Biochemistry},
  number    = {3},
  doi       = {10.1159/000447827},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164900},
  pages     = {1209-1228},
  year      = {2016},
  abstract  = {Background: Similar to tumor cells, activated T-lymphocytes generate ATP mainly by glycolytic degradation of glucose. Lymphocyte glucose uptake involves non-concentrative glucose carriers of the GLUT family. In contrast to GLUT isoforms, Na+-coupled glucose-carrier SGLT1 accumulates glucose against glucose gradients and is effective at low extracellular glucose concentrations. The present study explored expression and regulation of SGLT1 in activated murine splenic cytotoxic T cells (CTLs) and human Jurkat T cells. Methods: FACS analysis, immunofluorescence, confocal microscopy, chemiluminescence and Western blotting were employed to estimate SGLT1 expression, function and regulation in lymphocytes, as well as dual electrode voltage clamp in SGLT1 ± JAK3 expressing Xenopus oocytes to quantify the effect of janus kinase3 (JAK3) on SGLT1 function. Results: SGLT1 is expressed in murine CTLs and also in human Jurkat T cells. 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose uptake was significantly decreased by SGLT1-blocker phloridzin (0.2 mM) and by pharmacological inhibition of JAK3 with WHI-P131 (156 µM), WHI-P154 (11.2 µM) and JAK3 inhibitor VI (0.5 µM). Electrogenic glucose transport (Iglucose) in Xenopus oocytes expressing human SGLT1 was increased by additional expression of human wild type JAK3, active A568VJAK3 but not inactive K851AJAK3. Coexpression of JAK3 enhanced the maximal transport rate without significantly modifying affinity of the carrier. Iglucose in SGLT1+JAK3 expressing oocytes was significantly decreased by WHI-P154 (11.2 µM). JAK3 increased the SGLT1 protein abundance in the cell membrane. Inhibition of carrier insertion by brefeldin A (5 µM) in SGLT1+JAK3 expressing oocytes resulted in a decline of Iglucose, which was similar in presence and absence of JAK3. Conclusions: SGLT1 is expressed in murine cytotoxic T cells and human Jurkat T cells and significantly contributes to glucose uptake in those cells post activation. JAK3 up-regulates SGLT1 activity by increasing the carrier protein abundance in the cell membrane, an effect enforcing cellular glucose uptake into activated lymphocytes and thus contributing to the immune response.},
  language  = {en}
}
@article{SchmidtLiuLiuetal.2014,
  author    = {Schmidt, Sebastian and Liu, Guoxing and Liu, Guilai and Yang, Wenting and Honisch, Sabina and Pantelakos, Stavros and Stournaras, Christos and H{\"o}nig, Arnd and Lang, Florian},
  title     = {Enhanced Orai1 and STIM1 expression as well as store operated \(Ca^{2+}\) entry in therapy resistant ovary carcinoma cells},
  series = {Oncotarget},
  volume    = {5},
  journal   = {Oncotarget},
  number    = {13},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121423},
  pages     = {4799-810},
  year      = {2014},
  abstract  = {Mechanisms underlying therapy resistance of tumor cells include protein kinase Akt. Putative Akt targets include store-operated \(Ca^{2+}\)-entry (SOCE) accomplished by pore forming ion channel unit Orai1 and its regulator STIM1. We explored whether therapy resistant (A2780cis) differ from therapy sensitive (A2780) ovary carcinoma cells in Akt, Orai1, and STIM1 expression, \(Ca^{2+}\)-signaling and cell survival following cisplatin (100µM) treatment. Transcript levels were quantified with RT-PCR, protein abundance with Western blotting, cytosolic \(Ca^{2+}\)-activity ([\(Ca^{2+}\)]i) with Fura-2-fluorescence, SOCE from increase of [\(Ca^{2+}\)]i following \(Ca^{2+}\)-readdition after Ca2+-store depletion, and apoptosis utilizing flow cytometry. Transcript levels of Orai1 and STIM1, protein expression of Orai1, STIM1, and phosphorylated Akt, as well as SOCE were significantly higher in A2780cis than A2780 cells. SOCE was decreased by Akt inhibitor III (SH-6, 10µM) in A2780cis but not A2780 cells and decreased in both cell lines by Orai1 inhibitor 2-aminoethoxydiphenyl borate (2-ABP, 50µM). Phosphatidylserine exposure and late apoptosis following cisplatin treatment were significantly lower in A2780cis than A2780 cells, a difference virtually abolished by SH-6 or 2-ABP. In conclusion, Orai1/STIM1 expression and function are increased in therapy resistant ovary carcinoma cells, a property at least in part due to enhanced Akt activity and contributing to therapy resistance in those cells.},
  language  = {en}
}