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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
1999-5-20
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pubmed:abstractText |
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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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-142253,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-1521720,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-2521836,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-2526767,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-2526769,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-2881146,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-3155867,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-4295475,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-4339115,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-4921840,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-6108240,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-6272129,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-7643121,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-7744749,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-7752811,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-7924827,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-8080500,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-8109840,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-8147870,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-8348756,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-8620843,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-8643465,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-8876997,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-8887146,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-8911677,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-9012844,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-9144569,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-9207086,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-9299380,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-9308963,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-9334719,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-9390644,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-9390645,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-9584196,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-9670921,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-9740102,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-9778846,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-9795136,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-9804757,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-9822378,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-9832385,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-9837934,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10077636-9857092
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
16
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pubmed:volume |
96
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3059-64
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pubmed:dateRevised |
2010-9-10
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pubmed:meshHeading |
pubmed-meshheading:10077636-Animals,
pubmed-meshheading:10077636-DNA Damage,
pubmed-meshheading:10077636-Diabetes Mellitus, Experimental,
pubmed-meshheading:10077636-Enzyme Inhibitors,
pubmed-meshheading:10077636-Genetic Predisposition to Disease,
pubmed-meshheading:10077636-Mice,
pubmed-meshheading:10077636-Mice, Knockout,
pubmed-meshheading:10077636-Poly(ADP-ribose) Polymerases,
pubmed-meshheading:10077636-Streptozocin
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pubmed:year |
1999
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pubmed:articleTitle |
Poly(ADP-ribose) polymerase-deficient mice are protected from streptozotocin-induced diabetes.
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pubmed:affiliation |
Departments of Neuroscience, Pharmacology and Molecular Sciences, and Psychiatry, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.
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