Project/Area Number |
12671096
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Metabolomics
|
Research Institution | Tohoku University |
Principal Investigator |
SUZUKI Susumu Tohoku University Hospital, Lecturer, 医学部・附属病院, 講師 (70216399)
|
Co-Investigator(Kenkyū-buntansha) |
HIRAI Masashi Tohoku University Hospital, Research Associate, 医学部・附属病院, 助手 (80312578)
HINOKIO Yoshinori Tohoku University Hospital, Research Associate, 医学部・附属病院, 助手 (10282071)
|
Project Period (FY) |
2000 – 2001
|
Project Status |
Completed (Fiscal Year 2001)
|
Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
|
Keywords | Diabetes mellitus / Diabetic complication / Diabetic nephropathy / Diabetic retinopathy / Oxidative stress / Oxidative DNA damage / GC-MS / 8-oxo-deoxyguanosine / 8-OXO-deoxyguanosine / DNA損傷 / 活性酸素 |
Research Abstract |
There were several line of evidence to demonstrate a possible relationship oxidative DNA damages and diabetic complications. We demonstrated a significant relationship between the urinary and/or leukocyte 8-oxodG and insulin sensitivity in normal subjects and type 2 diabetic patients. We also demonstrated significant relationship between the urinary and/or leukocyte 8-oxodG and the severity of diabetic nephropathy and retinopathy in a cross-sectional study. We demonstrates a significant association between the urinary 8-oxodG levels and the development of nephropathy in a prospective study. This prospective study also demonstrates a significant association between the leukocyte 8-oxodG levels and the development of retinopathy. Thus, the study provides evidence that augmented oxidative stress has a primary role in the pathogenesis of diabetic nephropathy and retinopathy. We also developed the new assay system using gas-chromatography/mass spectrometry (GC/MS) to measure pyrimidine oxidation products, purine oxidation products, base deamination products, base chlorination products. Using this assay system, we have performed the precise characterization of oxidative DNA damages in diabetes mellitus and pathogenesis of diabetic complications.
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