title: Expression pattern of 12-lipoxygenase in human islets with type 1 diabetes and type 2 diabetes.
abstract: BACKGROUND
  Inflammation in the pancreas can cause β-cell stress, leading to diabetes development. Access to human pancreas tissues via the Network for Pancreatic Organ Donors with Diabetes (nPOD) has allowed characterization of pathways leading to this inflammation.
  
  
  OBJECTIVE
  12-Lipoxygenase (12-LO) induces inflammation and has been implicated in diabetes development. Our goal was to determine expression of 12-LO in human islets from control, autoantibody-positive, type 1 diabetic, and type 2 diabetic nPOD pancreas donors.
  
  
  METHODS
  Pancreas tissues from nPOD donors were examined by immunohistochemistry and immunofluorescence for islet expression of 12-LO in different subsets of islet cells.
  
  
  METHODS
  Donor pancreas samples were obtained from nPOD based on disease status (control, n = 7; autoantibody-positive, n = 8; type 1 diabetic, n = 17; or type 2 diabetic donors, n = 15).
  
  
  METHODS
  Determination of 12-LO expression within human islets served as the main outcome measure, including distinguishing which types of islet cells expressed 12-LO.
  
  
  RESULTS
  Islets from control participants (nondiabetic) lacked islet expression of 12-LO. Of donors in the other groups, 25% to 37% expressed islet 12-LO with a clear inverse relation between the numbers of β-cells and 12-LO(+) cells within islets of 12-LO(+) cases. 12-LO expression was not seen within macrophages, endothelial cells, α-cells, or β-cells, but only within cells expressing low levels of pancreatic polypeptide (PP) and increased levels of vimentin.
  
  
  CONCLUSIONS
  12-LO expression colocalizes within a specific type of islet PP(+) cell under prediabetic and diabetic conditions. The costaining of PP and vimentin suggests that 12-LO participates in the process leading to β-cell dedifferentiation in the islet.
authors.affiliation: Department of Internal Medicine (W.J.G., J.L.N., Y.M., J.L.N., Y.I.), Strelitz Diabetes Center, and Department of Microbiology and Molecular Cell Biology (M.A.M.), Eastern Virginia Medical School, Norfolk, Virginia 23507.
authors.forename: Wojciech J
authors.initials: WJ
authors.lastname: Grzesik
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Nadler
authors.forename: Yui
authors.initials: Y
authors.lastname: Machida
authors.forename: Jerry L
authors.initials: JL
authors.lastname: Nadler
authors.forename: Yumi
authors.initials: Y
authors.lastname: Imai
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Morris
mesh_terms: D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics* / Q000378:metabolism; D001323:Autoantibodies / Q000378:metabolism; D054337:Cell Dedifferentiation / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology; D016035:Pancreas Transplantation; D010191:Pancreatic Polypeptide / Q000378:metabolism; D014019:Tissue Donors; D014746:Vimentin / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D014746:Vimentin; D010191:Pancreatic Polypeptide; D001092:Arachidonate 12-Lipoxygenase