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Publication : Development of autoimmune diabetes in NOD mice is associated with the formation of peroxynitrite in pancreatic islet beta-cells.

First Author  Suarez-Pinzon WL Year  1997
Journal  Diabetes Volume  46
Issue  5 Pages  907-11
PubMed ID  9133563 Mgi Jnum  J:39970
Mgi Id  MGI:87312 Doi  10.2337/diab.46.5.907
Citation  Suarez-Pinzon WL, et al. (1997) Development of autoimmune diabetes in NOD mice is associated with the formation of peroxynitrite in pancreatic islet beta-cells. Diabetes 46(5):907-11
abstractText  Peroxynitrite (ONOO-) is a highly reactive oxidant species produced by the reaction of the free radicals superoxide (O(2).-) 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 beta-cells. Most of the beta-cells in islets from acutely diabetic NOD mice were NT+ (73 +/- 8%), whereas significantly fewer beta-cells were NT+ in islets from normoglycemic NOD mice (18 +/- 4%) and BALB/c mice (5 +/- 1%). Also, the percentage of beta-cells in islets from NOD mice (normoglycemic and diabetic) correlated inversely with the frequency of NT+ beta-cells. This study demonstrates for the first time that peroxynitrite, a reaction product of superoxide and nitric oxide, is formed in pancreatic islet beta-cells of NOD mice developing autoimmune diabetes. This suggests that both oxygen and nitrogen free radicals contribute to beta-cell destruction in IDDM via peroxynitrite formation in the islet beta-cells.
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