title: Cell death-inducing DFF45-like effector b (Cideb) is present in pancreatic beta-cells and involved in palmitate induced beta-cell apoptosis.
abstract: BACKGROUND
  Excessive accumulation of long-chain fatty acids in the pancreatic islets is associated with beta cell dysfunction and ultimately contributes to the pathogenesis of type 2 diabetes. It has been well proved that the cell death-inducing DFF45-like effector b (Cideb) is involved in cell apoptosis and lipid metabolism. However, the expression and function of Cideb in endocrine pancreas remain to be investigated.
  
  
  METHODS
  By using reverse transcript polymerase chain reaction, immunohistochemistry and Western blot, we observed the expression of Cideb in pancreas tissues and clonal beta-cell lines. The physiological role of Cideb was examined under the free fatty acid (FFA) administration and Cideb ribonucleic acid interference, and further analysis on apoptosis was measured by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling assay and caspase-3 activity. Nile red staining and quantitative evaluation of triglyceride were used to detect the lipid accumulation. The changes in esterification of FFA were traced by radiolabelled palmitate.
  
  
  RESULTS
  Cideb was abundantly expressed in pancreas and mainly localized in beta cells. FFAs, especially palmitate, induced an obvious increase of Cideb expression in beta cell lines. Adenoviral-mediated overexpression of Cideb increased the apoptosis, whereas ribonucleic acid interference-based Cideb depletion in beta-TC3 cells had no effect on apoptosis in normal condition. Palmitate supplementation led to beta cell lipoapoptosis, and Cideb silencing exacerbated the apoptosis induced by palmitate, reduced intracellular triglyceride content and aggravated FFA overload in beta cells.
  
  
  CONCLUSIONS
  The present results suggest that increased Cideb expression upon palmitate exposure may be involved in beta cell lipoapoptosis through its influence on conversion of FFAs to lipid esters in lipid droplets.
authors.affiliation: State Key Laboratory of Cancer Biology and Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.forename: Y
authors.initials: Y
authors.lastname: Song
authors.forename: L J
authors.initials: LJ
authors.lastname: Zhang
authors.forename: F F
authors.initials: FF
authors.lastname: Li
authors.forename: Y
authors.initials: Y
authors.lastname: Gu
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: W P
authors.initials: WP
authors.lastname: Dong
authors.forename: L
authors.initials: L
authors.lastname: Xue
authors.forename: L Y
authors.initials: LY
authors.lastname: Zhang
authors.forename: F
authors.initials: F
authors.lastname: Liu
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: L N
authors.initials: LN
authors.lastname: Jiang
authors.forename: J
authors.initials: J
authors.lastname: Ye
authors.forename: Q
authors.initials: Q
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D016175:B-Lymphocyte Subsets / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects*; D002460:Cell Line; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D006801:Humans; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D010168:Palmitates / Q000494:pharmacology*; D051381:Rats
chemical_list: D051017:Apoptosis Regulatory Proteins; C112511:CIDEB protein, human; C484761:Cideb protein, mouse; C572902:DFF45-like effector b, rat; D005230:Fatty Acids, Nonesterified; D010168:Palmitates