Poly(ADP-ribose) polymerase-deficient mice are protected from streptozotocin-induced diabetes
Poly(ADP-ribose) polymerase-deficient mice are protected from streptozotocin-induced diabetes
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DOI：
10.1073/pnas.96.6.3059
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发表时间：
1999-03-16
影响因子：
11.1
通讯作者：
Snyder, SH
中科院分区：
文献类型：
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作者：
Pieper, AA;Brat, DJ;Snyder, SH
链脲佐菌素（STZ）选择性地破坏胰腺产生胰岛素的β胰岛细胞，提供了I型糖尿病的模型，聚（adp -核糖）聚合酶（PARP）是一种核酶，其DNA链断裂导致其底物NAD（+）和ATP的过度激活，导致细胞能量消耗而死亡。研究显示stz处理小鼠胰岛DNA损伤和PARP的主要激活。这些小鼠的血糖增加了500%，胰岛受到严重损害。在纯合子靶向缺失PARP （PARP -/-）的小鼠中，血糖和胰岛结构正常，表明对STZ糖尿病几乎完全保护。部分保护发生在PARP +/-动物身上。因此，PARP激活可能参与了I型糖尿病的病理生理，PARP抑制剂可能提供治疗益处。
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.