title: Dysregulation of Hnf1b gene expression in cultured beta-cells in response to cytotoxic fatty acid.
abstract: BACKGROUND
  Increased levels of circulating fatty acids deriving from over-nutrition are thought to contribute to the progressive beta-cell failure associated with type 2 diabetes. Pancreatic beta-cells in culture are sensitive to exposure to long-chain saturated fatty acids (e.g. palmitate) which cause cytotoxicity, whereas the monounsaturated equivalents (e.g. palmitoleate) are cytoprotective.
  
  
  OBJECTIVE
  In this study we sought to determine whether of members of the hepatocyte nuclear factor (HNF) family of transcription factors, which are mutated in familial, young-onset, monogenic beta-cell diabetes, could play a role in fatty acid-mediated cytotoxicity in cultured beta-cells.
  
  
  METHODS
  We used real-time PCR to determine whether hepatocyte nuclear factor gene expression was altered in response to palmitate exposure in the BRIN-BD11 beta-cell line.
  
  
  RESULTS
  We found that the Hnf isoforms expressed in BRIN-BD11 cells are dysregulated by palmitate exposure. The expression of Hnf1b is specifically reduced by exposure to palmitate, and this response is prevented by co-incubation with palmitoleate.
  
  
  CONCLUSIONS
  Down-regulation of Hnf1b gene expression accompanies palmitate-mediated cytotoxicity in cultured beta-cells.
authors.affiliation: Institute of Biomedical and Clinical Science, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter, United Kingdom.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Johnstone
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Diakogiannaki
authors.forename: Shalinee
authors.initials: S
authors.lastname: Dhayal
authors.forename: Noel G
authors.initials: NG
authors.lastname: Morgan
authors.forename: Lorna W
authors.initials: LW
authors.lastname: Harries
mesh_terms: D000818:Animals; D002460:Cell Line; D003603:Cytotoxins / Q000494:pharmacology*; D005227:Fatty Acids / Q000494:pharmacology*; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D051539:Hepatocyte Nuclear Factor 1-beta / Q000235:genetics / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010168:Palmitates / Q000494:pharmacology; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D003603:Cytotoxins; D005227:Fatty Acids; D005229:Fatty Acids, Monounsaturated; C068755:Hnf1b protein, rat; D010168:Palmitates; D020033:Protein Isoforms; D051539:Hepatocyte Nuclear Factor 1-beta; C008757:palmitoleic acid