Clinical Immunotherapeutics

, Volume 2, Issue 4, pp 233–239 | Cite as

Nitric Oxide as an Inflammatory Mediator in Insulin-Dependent Diabetes Mellitus

A New Therapeutic Target?
  • Volker Burkart
  • Klaus-Dietrich Kröncke
  • Victoria Kolb-Bachofen
  • Hubert Kolb
Leading Article
First Online:

Summary

Recent studies in vitro and in vivo have demonstrated that the cellular mediator nitric oxide (NO) is involved in the destruction of insulin-producing pancreatic β-cells during the autoimmune pathogenesis of insulin-dependent diabetes mellitus. The primary source of islet cell toxic NO seems to be the inducible NO synthase of activated macrophages infiltrating the islets. NO rapidly induces the formation of DNA strand breaks in the islet cells. Consequently, the DNA repair enzyme poly(adenosine diphosphoribose) [poly(ADP-ribose)] polymerase (PARP) is activated to form ADP-ribose polymers from nicotinamide adenine dinucleotide (NAD+), thereby depleting the intracellular NAD+ pool to lethal levels.

These findings give rise to the development of strategies aiming at the protection of islet cells from NO toxicity in diabetes-susceptible individuals. However, general suppression of NO formation has only limited effects and acute systemic adverse effects cannot be excluded. At present the most promising approach seems to be the reduction of islet PARP activity by well-tolerated inhibitory agents.

Keywords

Nitric Oxide Islet Cell Pancreatic Islet Alloxan Pancreatic Islet Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Copyright information

© Adis International Limited 1994

Authors and Affiliations

  • Volker Burkart
    • 1
  • Klaus-Dietrich Kröncke
    • 2
  • Victoria Kolb-Bachofen
    • 2
  • Hubert Kolb
    • 1
  1. 1.Diabetes Research InstituteUniversity of DüsseldorfDüsseldorfGermany
  2. 2.Institute of ImmunobiologyUniversity of DüsseldorfDüsseldorfGermany

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