title: Tauroursodeoxycholate, a chemical chaperone, prevents palmitate-induced apoptosis in pancreatic β-cells by reducing ER stress.
abstract: BACKGROUND
  Free fatty acids (FFA) can have deleterious effects on β-cells and promote type 2 diabetes, a process known as lipotoxicity. Recently, the induction of endoplasmic reticulum (ER) stress is one mechanism proposed to contribute to the detrimental effects of FFA on β-cells. Tauroursodeoxycholic acid (TUDCA) has been reported to show cytoprotective effects by alleviating ER stress induced by some cytotoxic stimuli. The aim of this study was to investigate the effects of TUDCA on FFA (palmitate)-induced apoptosis and ER stress in rat islet β-cells.
  
  
  METHODS
  The rat pancreatic β-cell line INS-1 was cultured with palmitate (0.5 mM), or cultured togther with TUDCA (100 μM), Annexin V-fluorescein-isothiocyanate/propidium iodide flow cytometry was used to assess apoptosis in INS-1 cells. Cell viability was evaluated with MTT reduction conversion assay. The expressions of ER stress marker GRP78, ER stress-associated pro-apoptotic effectors CHOP and ATF4 were detected by Western blotting.
  
  
  RESULTS
  TUDCA significantly reduced palmitate-induced cell apoptosis and growth inhibition in INS-1 cells. TUDCA also attenuated palmitate-induced expressions of GRP78, CHOP and ATF4 in INS-1 cells.
  
  
  CONCLUSIONS
  Our results thus suggested that TUDCA could protect INS-1 cells from palmitate-induced injury, which might be due to the amelioration of ER stress and blocking the ATF4/CHOP signaling pathway.
authors.affiliation: Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhu
authors.forename: J J
authors.initials: JJ
authors.lastname: Zhong
authors.forename: J F
authors.initials: JF
authors.lastname: Jin
authors.forename: X M
authors.initials: XM
authors.lastname: Yin
authors.forename: H
authors.initials: H
authors.lastname: Miao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002756:Cholagogues and Choleretics / Q000494:pharmacology; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D018832:Molecular Chaperones / Q000494:pharmacology*; D019308:Palmitic Acid / Q000494:pharmacology*; D051381:Rats; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology*
chemical_list: D002756:Cholagogues and Choleretics; D004791:Enzyme Inhibitors; D018832:Molecular Chaperones; D019308:Palmitic Acid; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine