Peroxynitrite (ONOO−) is a highly reactive oxidant species produced by the reaction of the free radicals superoxide (O2·–) and nitric oxide (NO·). Here we report a marked increase in nitrotyrosine (NT), a marker of peroxynitrite, in islet cells from NOD mice developing spontaneous autoimmune diabetes. By using specific antibodies and immunohistochemical methods, we found that NT-positive cells were significantly more frequent in islets from acutely diabetic NOD mice (22 ± 6%) than in islets from normoglycemic NOD mice (7 ± 1%) and control BALB/c mice (2 ± 1%). The NT+ cells in islets were identified to be macrophages and also β-cells. Most of the β-cells in islets from acutely diabetic NOD mice were NT+ (73 ± 8%), whereas significantly fewer β-cells were NT+ in islets from normoglycemic NOD mice (18 ± 4%) and BALB/c mice (5 ± 1%). Also, the percentage of β-cells in islets from NOD mice (normoglycemic and diabetic) correlated inversely with the frequency of NT+ β-cells. This study demonstrates for the first time that peroxynitrite, a reaction product of superoxide and nitric oxide, is formed in pancreatic islet β-cells of NOD mice developing autoimmune diabetes. This suggests that both oxygen and nitrogen free radicals contribute to β-cell destruction in IDDM via peroxynitrite formation in the islet β-cells.
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May 01 1997
Development of Autoimmune Diabetes in NOD Mice Is Associated With the Formation of Peroxynitrite in Pancreatic Islet β-Cells
Wilma L Suarez-Pinzon;
Wilma L Suarez-Pinzon
Department of Medicine (W.L.S.-R, A.R.), University of Alberta, Edmonton, Alberta, Canada; and the Children's Hospital Medical Center, Division of Critical Care (C.S.)
Cincinnati, Ohio
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Casaba Szabó;
Casaba Szabó
Department of Medicine (W.L.S.-R, A.R.), University of Alberta, Edmonton, Alberta, Canada; and the Children's Hospital Medical Center, Division of Critical Care (C.S.)
Cincinnati, Ohio
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Alex Rabinovitch
Alex Rabinovitch
Department of Medicine (W.L.S.-R, A.R.), University of Alberta, Edmonton, Alberta, Canada; and the Children's Hospital Medical Center, Division of Critical Care (C.S.)
Cincinnati, Ohio
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Address correspondence and reprint requests to Alex Rabinovitch, MD, 430 Heritage Medical Research Centre, University of Alberta, Edmonton, Alberta, Canada, T6G 2S2. [email protected].
1
IFN-γ, γ-interferon; IL-1β, interleukin; iNOS, inducible nitric oxide synthase; LPS, lipopolysaccharide; mAb, monoclonal antibody; NT, nitrotyrosine; PARS, poly-ADP-ribose synthetase; PBS, phosphate-buffered saline; TNF-α, tumor necrosis factor-α.
Diabetes 1997;46(5):907–911
Article history
Received:
January 29 1997
Revision Received:
February 19 1997
Accepted:
February 19 1997
PubMed:
9133563
Citation
Wilma L Suarez-Pinzon, Casaba Szabó, Alex Rabinovitch; Development of Autoimmune Diabetes in NOD Mice Is Associated With the Formation of Peroxynitrite in Pancreatic Islet β-Cells. Diabetes 1 May 1997; 46 (5): 907–911. https://doi.org/10.2337/diab.46.5.907
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