title: Protective Effect of Heme Oxygenase-1 on High Glucose-Induced Pancreatic β-Cell Injury.
abstract: BACKGROUND
  Glucose toxicity that is caused by chronic exposure to a high glucose concentration leads to islet dysfunction and induces apoptosis in pancreatic β-cells. Heme oxygenase-1 (HO-1) has been identified as an anti-apoptotic and cytoprotective gene. The purpose of this study is to investigate whether HO-1 up-regulation when using metalloprotophyrin (cobalt protoporphyrin, CoPP) could protect pancreatic β-cells from high glucose-induced apoptosis.
  
  
  METHODS
  Reverse transcription-polymerase chain reaction was performed to analyze the CoPP-induced mRNA expression of HO-1. Cell viability of INS-1 cells cultured in the presence of CoPP was examined by acridine orange/propidium iodide staining. The generation of intracellular reactive oxygen species (ROS) was measured using flow cytometry. Glucose stimulated insulin secretion (GSIS) was determined following incubation with CoPP in different glucose concentrations.
  
  
  RESULTS
  CoPP increased HO-1 mRNA expression in both a dose- and time-dependent manner. Overexpression of HO-1 inhibited caspase-3, and the number of dead cells in the presence of CoPP was significantly decreased when exposed to high glucose conditions (HG). CoPP also decreased the generation of intracellular ROS by 50% during 72 hours of culture with HG. However, decreased GSIS was not recovered even in the presence of CoPP.
  
  
  CONCLUSIONS
  Our data suggest that CoPP-induced HO-1 up-regulation results in protection from high glucose-induced apoptosis in INS-1 cells; however, glucose stimulated insulin secretion is not restored.
authors: Division of Endocrinology and Metabolism, Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea.
authors: Eun-Mi
authors: EM
authors: Lee
authors: Young-Eun
authors: YE
authors: Lee
authors: Esder
authors: E
authors: Lee
authors: Gyeong Ryul
authors: GR
authors: Ryu
authors: Seung-Hyun
authors: SH
authors: Ko
authors: Sung-Dae
authors: SD
authors: Moon
authors: Ki-Ho
authors: KH
authors: Song
authors: Yu-Bae
authors: YB
authors: Ahn