title: Advanced glycation end-products induce injury to pancreatic beta cells through oxidative stress.
abstract: OBJECTIVE
  This study evaluated the direct effects of advanced glycation end-products (AGEs) on pancreatic β cells, including cellular viability, generation of reactive oxygen species (ROS) and insulin secretion, and also looked for the main source of ROS in INS-1 cells and the possible molecular mechanism(s) of cell injury by AGEs.
  
  
  METHODS
  INS-1 cells were cultured with 100, 200 and 500 mg/L of AGEs for specific periods of time. Cell apoptosis was determined by ELISA and real-time PCR assays. ROS were detected by DCFH-DA and MitoSOX Red probes with a flow cytometer, NADPH oxidase activity was measured by lucigenin chemiluminescence and MAPK phosphorylation was measured by Western blot tests.
  
  
  RESULTS
  Both cell apoptosis and ROS generation increased in AGE-treated cells in a dose-dependent way, and both the mitochondrial electron transport chain and NADPH oxidase pathway participated in ROS generation, although the role of the mitochondrial pathway was earlier and more important. AGEs exerted a toxic effect on insulin secretion that could be largely reversed by inhibiting ROS.
  
  
  CONCLUSIONS
  AGEs injured INS-1 cells by oxidative stress mainly through the mitochondrial pathway, although the JNK and p38 MAPK signaling pathways were also key modulators in ROS-mediated β-cell death.
authors.affiliation: Department of Endocrinology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665, Kong Jiang Road, Shanghai, 200092, China.
authors.forename: N
authors.initials: N
authors.lastname: Lin
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: Q
authors.initials: Q
authors.lastname: Su
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002470:Cell Survival; D002478:Cells, Cultured; D017127:Glycation End Products, Advanced / Q000009:adverse effects / Q000494:pharmacology*; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress; D010766:Phosphorylation; D051381:Rats; D017382:Reactive Oxygen Species / Q000009:adverse effects*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D017127:Glycation End Products, Advanced; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases