1993 Fiscal Year Final Research Report Summary
Molecular mechanisms of the developments of Graves' disease and diabetes mellitus ; O_2 production-DNA damage and their signal transductions
| Project/Area Number |
03807160
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
内分泌・代謝学
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| Research Institution | University of the Ryukyus (1993)
Shinshu University (1991-1992) |
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Principal Investigator |
TAKASU Nobuyuki Department of Medicine, University of the Ryukyus, Professor, 医学部, 教授 (20020927)
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| Project Period (FY) |
1991 – 1993
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| Keywords | Graves' disease / diabetes mellitus / thyroid / pancreatic B cells / O_2 production / DNA fragmentation / signal transduction / autoimmune endocrine diseases |
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| Research Abstract |
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.
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