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

被引：255

作者：

Pieper, AA

Brat, DJ

Krug, DK

Watkins, CC

Gupta, A

Blackshaw, S

Verma, A

Wang, ZQ

Snyder, SH

机构：

[1] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA

[3] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA

[4] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA

[5] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA

[6] Int Agcy Res Canc, F-69008 Lyon, France

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1999年 / 96卷 / 06期

关键词：

D O I：

10.1073/pnas.96.6.3059

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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. me 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.

引用

页码：3059 / 3064

页数：6

共 47 条

[1] STREPTOZOTOCIN - MECHANISMS OF ACTION - PROCEEDINGS OF A WORKSHOP HELD ON 21 JUNE 1980, WASHINGTON, DC [J].