title: Exendin-4 regulates the expression of the ATP-binding cassette transporter A1 via transcriptional factor PREB in the pancreatic β cell line.
abstract: BACKGROUND
  PRL regulatory element-binding (PREB) protein is a transcription factor that regulates insulin promoter activity in the rat anterior pituitary. The PREB protein is expressed not only in the anterior pituitary but also in pancreatic β cells. Previously, we have reported that PREB plays an important role in glucose-mediated insulin gene expression in pancreatic β cells. The ATP-binding cassette transporter A1 (ABCA1) in pancreatic β cells influences insulin secretion and glucose homeostasis. Exendin-4 (Ex-4), a longacting agonist of the glucagon-like peptide 1, stimulates ABCA1 expression in pancreatic β cells.
  
  
  OBJECTIVE
  In this study, we examined the role played by PREB in Ex-4-induced ABCA1 expression in pancreatic β cells.
  
  
  METHODS
  PREB mRNA and protein expression were evaluated in pancreatic β cell line (INS-1 cells) treated with Ex-4 (10 nM).
  
  
  RESULTS
  Ex-4 stimulated PREB protein and mRNA expression in INS-1 cells. PREB stimulated the activity of the luciferase reporter protein that was under the control of the ABCA1 promoter. Chromatin immunoprecipitation assay showed that PREB mediates its transcriptional activity by directly binding to the ABCA1 promoter region. Finally, we used small interfering RNA to inhibit PREB expression in the cells and demonstrated that the knockdown of PREB expression attenuated the effects of Ex-4 on ABCA1 expression.
  
  
  CONCLUSIONS
  PREB mediates Ex-4-stimulated transcription of the ABCA1 gene in pancreatic β cells.
authors.affiliation: Department of diagnostic pathology, Kagawa University, Miki-cho, Kita-gun, Kagawa, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Miyai
authors.forename: K
authors.initials: K
authors.lastname: Murao
authors.forename: H
authors.initials: H
authors.lastname: Imachi
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: Y
authors.initials: Y
authors.lastname: Nishiuchi
authors.forename: H
authors.initials: H
authors.lastname: Masugata
authors.forename: H
authors.initials: H
authors.lastname: Iwama
authors.forename: Y
authors.initials: Y
authors.lastname: Kushida
authors.forename: T
authors.initials: T
authors.lastname: Ishida
authors.forename: R
authors.initials: R
authors.lastname: Haba
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000077270:Exenatide; D017930:Genes, Reporter; D005947:Glucose / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D010455:Peptides / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D014688:Venoms / Q000494:pharmacology*
chemical_list: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D004268:DNA-Binding Proteins; D020662:Guanine Nucleotide Exchange Factors; D007328:Insulin; D010455:Peptides; C485592:Preb protein, rat; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014157:Transcription Factors; D014688:Venoms; D000077270:Exenatide; D005947:Glucose