Burkart V, Wang Z Q, Radons J, Heller B, Herceg Z, Stingl L, Wagner E F, Kolb H
Diabetes Research Institute at the Heinrich Heine University Düsseldorf, Germany.
Nat Med. 1999 Mar;5(3):314-9. doi: 10.1038/6535.
Human type 1 diabetes results from the selective destruction of insulin-producing pancreatic beta cells during islet inflammation. Cytokines and reactive radicals released during this process contribute to beta-cell death. Here we show that mice with a disrupted gene coding for poly (ADP-ribose) polymerase (PARP-/- mice) are completely resistant to the development of diabetes induced by the beta-cell toxin streptozocin. The mice remained normoglycemic and maintained normal levels of total pancreatic insulin content and normal islet ultrastructure. Cultivated PARP-/- islet cells resisted streptozocin-induced lysis and maintained intracellular NAD+ levels. Our results identify NAD+ depletion caused by PARP activation as the dominant metabolic event in islet-cell destruction, and provide information for the development of strategies to prevent the progression or manifestation of the disease in individuals at risk of developing type 1 diabetes.
人类1型糖尿病是由胰岛炎症期间胰岛素分泌胰腺β细胞的选择性破坏所致。在此过程中释放的细胞因子和活性自由基会导致β细胞死亡。我们在此表明，编码聚（ADP - 核糖）聚合酶的基因被破坏的小鼠（PARP - / - 小鼠）对β细胞毒素链脲佐菌素诱导的糖尿病发展完全具有抗性。这些小鼠保持血糖正常，胰腺胰岛素总量水平正常，胰岛超微结构正常。培养的PARP - / - 胰岛细胞可抵抗链脲佐菌素诱导的裂解并维持细胞内NAD + 水平。我们的结果确定由PARP激活引起的NAD + 耗竭是胰岛细胞破坏中的主要代谢事件，并为制定预防策略提供信息，以防止1型糖尿病高危个体中疾病的进展或表现。
