title: Decreased Expression and Induced Nucleocytoplasmic Translocation of Pancreatic and Duodenal Homeobox 1 in INS-1 Cells Exposed to High Glucose and Palmitate.
abstract: BACKGROUND
  Type 2 diabetes mellitus (T2DM) is often accompanied by increased levels of circulating fatty acid. Elevations in fatty acids and glucose for prolonged periods of time have been suggested to cause progressive dysfunction or apoptosis of pancreatic beta cells in T2DM. However, the precise mechanism of this adverse effect is not well understood.
  
  
  METHODS
  INS-1 rat-derived insulin-secreting cells were exposed to 30 mM glucose and 0.25 mM palmitate for 48 hours.
  
  
  RESULTS
  The production of reactive oxygen species increased significantly. Pancreatic and duodenal homeobox 1 (Pdx1) expression was down-regulated, as assessed by reverse transcription-polymerase chain reaction and Western blot analyses. The promoter activities of insulin and Pdx1 were also diminished. Of note, there was nucleocytoplasmic translocation of Pdx1, which was partially prevented by treatment with an antioxidant, N-acetyl-L-cysteine.
  
  
  CONCLUSIONS
  Our data suggest that prolonged exposure of beta cells to elevated levels of glucose and palmitate negatively affects Pdx1 expression via oxidative stress.
authors.affiliation: Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Gyeong Ryul
authors.initials: GR
authors.lastname: Ryu
authors.forename: Jun Mo
authors.initials: JM
authors.lastname: Yoo
authors.forename: Esder
authors.initials: E
authors.lastname: Lee
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Ko
authors.forename: Yu-Bae
authors.initials: YB
authors.lastname: Ahn
authors.forename: Ki-Ho
authors.initials: KH
authors.lastname: Song