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Poly(ADP-ribose) polymerase-deficient mice are protected from streptozotocin-induced diabetes
Open accessAbstract
Streptozotocin (STZ) selectively destroys insulin-producing beta islet cells of the pancreas providing a model of type I diabetes. Poly(ADP-ribose) polymerase (PARP) is a nuclear enzyme whose overactivation by DNA strand breaks depletes its substrate NAD + and then ATP, leading to cellular death from energy depletion. We demonstrate DNA damage and a major activation of PARP in pancreatic islets of STZ-treated mice. These mice display a 500% increase in blood glucose and major pancreatic islet damage. In mice with homozygous targeted deletion of PARP (PARP −/−), blood glucose and pancreatic islet structure are normal, indicating virtually total protection from STZ diabetes. Partial protection occurs in PARP +/− animals. Thus, PARP activation may participate in the pathophysiology of type I diabetes, for which PARP inhibitors might afford therapeutic benefit.
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Citations
Cited by
Ying, W. (2008) · Antioxidants & Redox Signaling · doi:10.1089/ars.2007.1672 · Cited by 1,494
The secret life of NAD+: an old metabolite controlling new metabolic signaling pathways
Houtkooper, R. H., Cantó, C., Wanders, R. J., & Auwerx, J. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0026 · Cited by 899
Diabetic neuropathy and oxidative stress
Pop-Busui, R., Sima, A., & Stevens, M. (2006) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.625 · Cited by 286
ARTD1/PARP1 Negatively Regulates Glycolysis by Inhibiting Hexokinase 1 Independent of NAD+ Depletion
Fouquerel, E., Goellner, E. M., Yu, Z., Gagné, J.-P., Barbi de Moura, M., Feinstein, T., Wheeler, D., Redpath, P., Li, J., Romero, G., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.08.036 · Cited by 212
Sources and implications of NADH/NAD+ redox imbalance in diabetes and its complications
Yan, L.-J., Wu, J., Jin, Z., & Zheng, H. (2016) · Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy · doi:10.2147/dmso.s106087 · Cited by 198
Metadata
- Authors
- Pieper, A. A., Brat, D. J., Krug, D. K., Watkins, C. C., Gupta, A., Blackshaw, S., Verma, A., Wang, Z.-Q., & Snyder, S. H.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1999-03-16
- Volume
- 96
- Issue
- 6
- Pages
- 3059-3064
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2142114374
- Cited by
- 298
- References
- 0
- FWCI
- 24.98
- Type
- journal article
- Language
- en
- Open access
- green
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- The paper
- Pieper, A. A., Brat, D. J., Krug, D. K., Watkins, C. C., Gupta, A., Blackshaw, S., Verma, A., Wang, Z.-Q., & Snyder, S. H. (1999). Poly(ADP-ribose) polymerase-deficient mice are protected from streptozotocin-induced diabetes. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.96.6.3059
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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