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- Title
Mice lacking the poly(ADP-ribose) polymerase gene are resistant to pancreatic beta-cell destruction and diabetes development induced by streptozocin.
- Authors
Burkart, Volker; Wang, Zhao-Qi; Radons, Jürgen; Heller, Birgit; Herceg, Zdenko; Stingl, Laura; Wagner, Erwin F.; Kolb, Hubert
- Abstract
Human type I diabetes results from the selective destruction of insulin-producing pancreatic beta cells during islet inflammation. Cytokines and reactive radicals released during this process contribute to beta-cell death. Here we show that mice with a disrupted gene coding for poly (ADP-ribose) polymerase (PARP[sup -I-] mice) are completely resistant to the development of diabetes induced by the beta-cell toxin streptozocin. The mice remained normoglycemic and maintained normal levels of total pancreatic insulin content and normal islet ultrastructure. Cultivated PARP[sup -/] islet cells resisted streptozocin-induced lysis and maintained intracellular NAD[sup +] levels. Our results identify NAD[sup +] depletion caused by PARP activation as the dominant metabolic event in islet-cell destruction, and provide information for the development of strategies to prevent the progression or manifestation of the disease in individuals at risk of developing type 1 diabetes.
- Subjects
RIBOSE; PANCREATIC beta cells; STREPTOZOTOCIN; LABORATORY mice
- Publication
Nature Medicine, 1999, Vol 5, Issue 3, p314
- ISSN
1078-8956
- Publication type
Article
- DOI
10.1038/6535