title: Amino acid-induced gene expression profiling in clonal β-cell line INS-1E cells.
abstract: BACKGROUND
  There is abundant evidence that glucotoxicity and lipotoxicity contribute to impaired β-cell function in type 2 diabetes. Interestingly, amino acid (AA) derangement is also a characteristic part of the diabetic state. The acute effects of AA on pancreatic β-cell function have been widely explored; however, to our knowledge, the chronic effects of AA, e.g. proline (Pro), homocysteine (Hcy), and leucine (Leu), on pancreatic β-cell function and integrity have not yet been studied. We aimed to investigate global alterations in β-cell gene expression after long-term exposure of clonal INS-1E cells to elevated level of specific AA in vitro.
  
  
  METHODS
  Global gene expression profiling was performed to characterize genes differently modified by Pro, Hcy, and Leu, respectively, in INS-1E cells.
  
  
  RESULTS
  Gene expression profiling revealed significant changes in INS-1E cell mRNAs involved in the control of several aspects of β-cell function, e.g. epigenetic regulation of gene expression, metabolism, innate and adaptive immune responses, cellular signalling, protein synthesis, apoptosis, and cellular stress response. After 72 h, INS-1E cells were differentially regulated (≥1.5- or ≤ -1.5-fold) by Pro (295 transcripts), Hcy (301 transcripts), and Leu (701 transcripts). It appears that Hcy effects changes opposite to those induced by Leu and/or Pro.
  
  
  CONCLUSIONS
  AA appears to participate in and to influence many physiological processes including those involved in cholesterol metabolism, immune responses, and oxidative phosphorylation. Whether such events promote the β-cell dysfunction and the β-cell failure in diabetes remains to be elucidated. Our data strongly indicate that AA elevation may take part in the progressive development of type 2 diabetes.
authors.affiliation: Department of Endocrinology and Metabolism MEA, Aarhus University Hospital, Aarhus Sygehus THG, Tage-Hansens Gade 2, Aarhus C, Denmark.
authors.forename: Zhenping
authors.initials: Z
authors.lastname: Liu
authors.forename: Yonglun
authors.initials: Y
authors.lastname: Luo
authors.forename: Per Bendix
authors.initials: PB
authors.lastname: Jeppesen
authors.forename: Søren
authors.initials: S
authors.lastname: Gregersen
authors.forename: Kjeld
authors.initials: K
authors.lastname: Hermansen
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D006710:Homocysteine / Q000494:pharmacology*; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D007930:Leucine / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D011392:Proline / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D006710:Homocysteine; D011392:Proline; D007930:Leucine