Molecular mechanisms of the developments of Graves' disease and diabetes mellitus ; O_2 production-DNA damage and their signal transductions

Graves病合并糖尿病患者较多。Graves病和糖尿病都是自身免疫性疾病。然而，Graves病和糖尿病发生的分子机制尚不清楚。因此，我们试图揭示Graves病和糖尿病发生的分子机制，并发现O_2的产生及其DNA断裂在这两种疾病的发生发展中起着非常重要的作用。我们还研究了O_2产生和DNA断裂的信号转导系统。我们培养了甲状腺细胞和胰岛，并进行了许多实验。我们为糖尿病发生的分子机制提供了明确的证据。链脲佐菌素和四氧嘧啶具有最强的致糖尿病作用，已被用于诱导实验性糖尿病。DNA断裂在糖尿病的发展中起着重要的作用。我们的体外和体内实验表明，链脲佐菌素和四氧嘧啶刺激H_2O_2的产生，导致DNA断裂。链脲佐菌素和四氧嘧啶通过以下生化事件诱导糖尿病；链脲佐剂和四氧嘧啶->H_2O_2生成->DNA断裂->糖尿病。Ca作为一个信号转导系统，在链脲佐菌素和四氧嘧啶->H_2O_2生成->DNA断裂->糖尿病中起重要作用。

There are many patients with Graves' disease and diabetes mellitus. Both Graves' disease and diabetes mellitus are autoimmune diseases. However, we do not know the molecular mechanisms of the developments of Graves' disease and diabetes mellitus. Thus we intended to reveal the molecular mechanisms of the developments of Graves' disease and diabetes mellitus, and found that O_2 production and consequent DNA fragmentation playd very important roles in the development of both diseases. We also studied the signal transduction systems of O_2 production and DNA fragmentation. We cultured thyroid cells and pancreatic islets and conducted many experiments.We obtained a clear evidence for the molecular mechanism of the development of diabetes mellitus. Streptozotocin and alloxan exhibit the most potent diabetogenecity, and have been used for induction of experimental diabetes mellitus. DNA fragmentation plays an important role for the development of diabetes. Our in vitro and vivo experiments demonstrated that streptozotocin and alloxan stimulated H_2O_2 generation, which induced DNA fragmentation. Streptozotocin and alloxan induce diabetes through the following biochemical events ; streptozotocin and alloxan->H_2O_2 generation->DNA fragmentation->diabetes. As a signal transduction system, Ca plays an important role in streptozotocin and alloxan->H_2O_2 generation->DNA fragmentation->diabetes.