An inhibitor of inducible nitric oxide synthase and scavenger of peroxynitrite prevents diabetes development in NOD mice

Wilma L. Suarez-Pinzon, Jon G. Mabley, Ken Strynadka, Robert F. Power, Csaba Szabo, Alex Rabinovitch

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

Peroxynitrite (ONOO-) is a highly reactive oxidant produced by the interaction of the free radicals superoxide (O2 ·-) and nitric oxide (NO·). In a previous study, we found that peroxynitrite is formed in islet β-cells of nonobese diabetic (NOD) mice. Here, we report that guanidinoethyldisulphide (GED), a selective inhibitor of inducible nitric oxide synthase (iNOS) and scavenger of peroxynitrite prevents diabetes in NOD mice. GED treatment of female NOD mice, starting at age 5 weeks, delayed diabetes onset (from age 12 to 22 weeks) and significantly decreased diabetes incidence at 30 weeks (from 80% to 17%). GED did not prevent pancreatic islet infiltration by leukocytes; however, β-cells that stained positive for nitrotyrosine (a marker of peroxynitrite) were significantly decreased in islets of GED-treated mice (1±1%) compared with vehicle-treated mice (30±9%). In addition, GED significantly inhibited nitric oxide and nitrotyrosine formation and decreased destruction of β-cells in NOD mouse islets incubated in vitro with the combination of proinflammatory cytokines interleukin 1-beta (IL-1β), tumour necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ). These findings indicate that both superoxide and nitric oxide radicals contribute to islet β-cell destruction in autoimmune diabetes via peroxynitrite formation in the β-cells.

Original languageEnglish (US)
Pages (from-to)449-455
Number of pages7
JournalJournal of Autoimmunity
Volume16
Issue number4
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Inbred NOD Mouse
Peroxynitrous Acid
Nitric Oxide Synthase Type II
Islets of Langerhans
Nitric Oxide
Superoxides
Type 1 Diabetes Mellitus
Interleukin-1beta
Age of Onset
Interferon-alpha
Oxidants
Interferon-gamma
Free Radicals
Leukocytes
Tumor Necrosis Factor-alpha
bis(2-guanidinoethyl)disulfide
Cytokines
Incidence

Keywords

  • Free radicals
  • Insulitis
  • Nitric oxide
  • NOD mice
  • Peroxynitrite

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

An inhibitor of inducible nitric oxide synthase and scavenger of peroxynitrite prevents diabetes development in NOD mice. / Suarez-Pinzon, Wilma L.; Mabley, Jon G.; Strynadka, Ken; Power, Robert F.; Szabo, Csaba; Rabinovitch, Alex.

In: Journal of Autoimmunity, Vol. 16, No. 4, 2001, p. 449-455.

Research output: Contribution to journalArticle

Suarez-Pinzon, Wilma L. ; Mabley, Jon G. ; Strynadka, Ken ; Power, Robert F. ; Szabo, Csaba ; Rabinovitch, Alex. / An inhibitor of inducible nitric oxide synthase and scavenger of peroxynitrite prevents diabetes development in NOD mice. In: Journal of Autoimmunity. 2001 ; Vol. 16, No. 4. pp. 449-455.
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