title: Erythropoietin protects pancreatic β-cell line NIT-1 cells against cytokine-induced apoptosis via phosphatidylinositol 3-kinase/Akt signaling.
abstract: OBJECTIVE
  Erythropoietin (EPO) is a cytokine that regulates the proliferation, differentiation, and survival of erythroid progenitor cells. EPO has recently been demonstrated to have a tissue-protective role by mediating anti-apoptotic signals through the erythropoietin receptor (EPOR) in various tissues, including brain, liver, and heart. We have previously examined pancreatic β-cell line NIT-1 cells for the expression of EPOR by real-time PCR and determined that these cells were protected by EPO against cytokine-induced apoptosis. The precise underlying anti-apoptotic mechanisms in pancreatic β-cells are poorly understood. The purpose of this study is to examine erythropoietin receptor expression in the NIT-1 pancreatic beta-cell line and the intracellular pathway related with its anti-apoptosis effect in NIT-1 cells.
  
  
  METHODS
  we examined the expression of EPOR by western blot. We investigate the role of erythropoietin in the survival of these cells, and whether the PI3K/AKT pathway is involved in this protective process.
  
  
  RESULTS
  NIT-1 cells expressed EPOR and, in the presence of certain cytokines, exposure of NIT-1 cells to recombinant human erythropoietin (rhEPO) significantly improved the impaired insulin secretion and inhibited cytokine-induced apoptosis. RhEPO caused a rapid activation of Akt and increased expression of Bcl-2. The protective anti-apoptotic effect of rhEPO was significantly abolished by a specific phosphatidylinositol 3-kiniase (PI3K) inhibitor, LY294002.
  
  
  CONCLUSIONS
  Our findings indicate that EPOR is expressed in pancreatic β-cell line NIT-1 cells and suggest that EPO may act as a survival factor requiring the PI3K/Akt pathway.
authors.affiliation: Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Shuai
authors.forename: Ji
authors.initials: J
authors.lastname: Zhang
authors.forename: Jinghui
authors.initials: J
authors.lastname: Zhang
authors.forename: Junhui
authors.initials: J
authors.lastname: Xie
authors.forename: Muxun
authors.initials: M
authors.lastname: Zhang
authors.forename: Yikai
authors.initials: Y
authors.lastname: Yu
authors.forename: Liming
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004921:Erythropoietin / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000502:physiology*; D051379:Mice; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D051381:Rats; D017467:Receptors, Erythropoietin / Q000032:analysis / Q000502:physiology; D011994:Recombinant Proteins; D015398:Signal Transduction / Q000502:physiology
chemical_list: D016207:Cytokines; D007328:Insulin; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D017467:Receptors, Erythropoietin; D011994:Recombinant Proteins; D004921:Erythropoietin; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt