title: Increase of INS-1 cell apoptosis under glucose fluctuation and the involvement of FOXO-SIRT pathway.
abstract: OBJECTIVE
  Variations of blood glucose level have been reported to be more harmful than sustained high glucose, but the effects on pancreatic β-cells have not yet been clarified. FOXO transcription factors are important for cell fate. We tried to clarify the effect of glucose variability on INS-1 cells, and the potential mechanisms related with FOXO-SIRT pathway.
  
  
  METHODS
  INS-1 cells were exposed to control, SHG (sustained high glucose) or IHG (intermittent high glucose) alternating every 12 h for 5 days.
  
  
  RESULTS
  INS-1 cells in SHG showed lower apoptosis and higher GSIS than IHG. Deacetylated FOXO and binding with SIRT were higher in SHG than IHG. Administration of PI3K inhibitor and/or SIRT inhibitor increased apoptosis and decreased Mn-SOD and Bcl-2 in SHG.
  
  
  CONCLUSIONS
  [corrected] IHG was more harmful to INS-1 cells than SHG. The degree of phosphorylation and acetylation of FOXO transcription factors were different between SHG and IHG, which might be one mechanism of increased INS-1 cell apoptosis in IHG.
authors.affiliation: Molecular Therapy Lab, Paik Institute for Clinical Research, Inje University, Busan, Republic of Korea.
authors.forename: Mikyung
authors.initials: M
authors.lastname: Kim
authors.forename: Hyesuk
authors.initials: H
authors.lastname: Chung
authors.forename: Changsin
authors.initials: C
authors.lastname: Yoon
authors.forename: Eunju
authors.initials: E
authors.lastname: Lee
authors.forename: Taenyun
authors.initials: T
authors.lastname: Kim
authors.forename: Taekyoon
authors.initials: T
authors.lastname: Kim
authors.forename: Minjeong
authors.initials: M
authors.lastname: Kwon
authors.forename: Soonhee
authors.initials: S
authors.lastname: Lee
authors.forename: Byoungdoo
authors.initials: B
authors.lastname: Rhee
authors.forename: Jeonghyun
authors.initials: J
authors.lastname: Park
mesh_terms: D000107:Acetylation; D000818:Animals; D017209:Apoptosis; D002470:Cell Survival / Q000235:genetics; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation; D051381:Rats; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D000071161:Forkhead Box Protein O1
chemical_list: D051858:Forkhead Transcription Factors; D005947:Glucose; D007328:Insulin; D009419:Nerve Tissue Proteins; D056564:Sirtuin 1; D014157:Transcription Factors; C074639:Foxo1 protein, rat; D000071161:Forkhead Box Protein O1; C488368:Sirt1 protein, rat