2001 Fiscal Year Final Research Report Summary
Development of a new assay method for oxidative DNA damages in diabetes
| Project/Area Number |
12671096
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Tohoku University |
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Principal Investigator |
SUZUKI Susumu Tohoku University Hospital, Lecturer, 医学部・附属病院, 講師 (70216399)
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| 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)
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| Project Period (FY) |
2000 – 2001
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| Keywords | Diabetes mellitus / Diabetic complication / Diabetic nephropathy / Diabetic retinopathy / Oxidative stress / Oxidative DNA damage / GC-MS / 8-oxo-deoxyguanosine |
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| 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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[Publications] L. J. Baier, P. A. Permana, M. Traurig, A. Dobberfuhl, C. Wiedrich, J. Sutherland, P. Thuillez, G. Luczy-Bachman, M. Hara, Y. Horikawa, Y. Hinokio, R. L. Hanson, C. Bogardus: "Mutations in the genes for hepatocyte nuclear factor (HNF)-1alpha, -4alpha, -1beta, and -3beta ; the dimerization cofactor of HNF-1 ; and insulin promoter factor 1 are not common causes of early-onset type 2 diabetes in Pima Indians"Diabetes Care. 23. 302-304 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Y. Horikawa, N. Oda, N. J. Cox, X. Li, M. Orho-Melander, M. Hara, Y. Hinokio. T. H. Lindner, H. Mashima, P. E. Schwarz, L. del Bosque-Plata, Y. Oda, I, Yoshiuchi, S. Colilla, K. S. Polonsky, S. Wei, P. Concannon, N. Iwasaki, J. Schulze, L. J. Baier, C. Bogardus, L. Groop, E. Boerwinkle, C. L. Hanis, G. I. Bell: "Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus"Nature Genet. 26. 163-175 (2000)
Description
「研究成果報告書概要(欧文)」より
