title: The Effects of Glyburide on Apoptosis and Endoplasmic Reticulum Stress in INS-1 Cells in a Glucolipotoxic Condition.
abstract: BACKGROUND
  β-cell death due to endoplasmic reticulum (ER) stress has been regarded as an important pathogenic component of type 2 diabetes. The possibility has been suggested that sulfonylurea, currently being used as one of the main oral hypoglycemic agents of type 2 diabetes, increases ER stress, which could lead to sulfonylurea failure. The authors of the present study examined ER stress of β-cells in a glucolipotoxic condition using glyburide (GB) in an environment mimicking type 2 diabetes.
  
  
  METHODS
  Apoptosis was induced by adding various concentrations of GB (0.001 to 200 µM) to a glucolipotoxic condition using 33 mM glucose, and the effects of varied concentrations of palmitate were evaluated via annexin V staining. The markers of ER stress and pro-apoptotic markers were assessed by Western blotting and semi-quantitative reverse transcription-polymerase chain reaction. Additionally, the anti-apoptotic markers were evaluated.
  
  
  RESULTS
  Addition of any concentration of GB in 150 µM palmitate and 33 mM glucose did not increase apoptosis. The expression of phosphorylated eukaryotic initiation factor (eIF-2α) was increased and cleaved caspase 3 was decreased by adding GB to a glucolipotoxic condition. However, other ER stress-associated markers such as Bip-1, X-box binding protein-1, ATF-4 and C/EBP-homologous protein transcription factor and anti-apoptotic markers phosphor-p85 phosphatidylinositol 3-kinase and phosphorylation of Akt did not change significantly.
  
  
  CONCLUSIONS
  GB did not show further deleterious effects on the degree of apoptosis or ER stress of INS-1 cells in a glucolipotoxic condition. Increased phosphorylation of eIF-2α may attenuate ER stress for adaptation to increased ER protein load.
authors: Paik Diabetes Center, Department of Internal Medicine, Inje University College of Medicine, Busan, Korea.
authors: Min Jeong
authors: MJ
authors: Kwon
authors: Hye Suk
authors: HS
authors: Chung
authors: Chang Shin
authors: CS
authors: Yoon
authors: Jung Hae
authors: JH
authors: Ko
authors: Hae Jung
authors: HJ
authors: Jun
authors: Tae Kyun
authors: TK
authors: Kim
authors: Soon Hee
authors: SH
authors: Lee
authors: Kyung Soo
authors: KS
authors: Ko
authors: Byoung Doo
authors: BD
authors: Rhee
authors: Mi Kyung
authors: MK
authors: Kim
authors: Jeong Hyun
authors: JH
authors: Park