Poly(ADP-ribose) polymerase-deficient mice are protected from streptozotocin-induced diabetes

Andrew A. Pieper, Daniel J. Brat, David K. Krug, Crystal C. Watkins, Alok Gupta, Seth Blackshaw, Ajay Verma, Zhao Qi Wang, Solomon H. Snyder*

*Corresponding author for this work

Research output: Contribution to journalArticle

271 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)3059-3064
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number6
StatePublished - Mar 16 1999

ASJC Scopus subject areas

  • Genetics
  • General

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