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Development of a new assay method for oxidative DNA damages in diabetes

Research Project

Project/Area Number 12671096
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Metabolomics
Research InstitutionTohoku 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)
KeywordsDiabetes 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.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] M.Hirai: "Variations in vitamin D-binding protein (group-specific component protein) are associated with fasting plasma insulin levels in Japanese with normal glucose tolerance"J Clin Endocrinol Metab. 85. 1951-1953 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] M.Chiba: "Tyrosine hydroxylase gene microsatellite polymorphism associated with insulin resistance in depressive disorder"Metabolism. 49. 1145-1149 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K.komatsu: "Cre-loxP-mediated bax gene activation reduces growth rate and increases sensitivity to chemotherapeutic agents in human gastric cancer cells"Cancer Gene Ther. 7. 885-892 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] F.Okamura: "Insulin resistance in patients with depression and its changes during the clinical course of depression : minimal model analysis"Metabolism. 49. 1255-1260 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] L.J.Baier: "Mutations in the genes for hepatocyte nuclear factor (HNF)-lalpha,-4alpha,-ibeta, and-3beta ; the dimerization cofactor of HNF-1;and insulin promoter factor 1 are not common causes of early-onset type2 diabetes in Pima Indians"Diabetes Care. 23. 302-304 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y.Hinokio: "Beta-cell transcription factors and diabete : no evidence for diabetes-associated mutations in the hepatocyte nuclear factor-3beta gene(HNF3B)in Japanese patients with maturity-onset diabetes of the young"Diabetes. 49. 302-305 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A.Abderrahmani: "Genetic variation in the hepatocyte nuclear factor-3beta gene (HNF3B) does not contribute to maturity-onset diabetes of the young in Frech Caucasians"Diabetes. 49. 306-308 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y.Horikawa: "Genetic variation in the gene encoding calpain-lO is associated with type2 diabetes mellitus"Nature Genet. 26. 163-175 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] M. Hirai, S. Suzuki, Y. Hinokio, A. Hirai, M. Chiba, H. Akai, C. Suzuki, T. Toyota: "Variations in vitamin D-binding protein (group-specific component protein) are associated with fasting plasma insulin levels in Japanese with normal glucose tolerance"J Clin Endocrinol Metab. 85. 1951-1953 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] M. Chiba, S. Suzuki, Y. Hinokio, M. Hirai, Y. Satoh, A. Tashiro, A. Utsumi, T. Awata, M. Hongo, T. Toyota: "Tyrosine hydroxylase gene microsatellite polymorphism associated with insulin resistance in depressive disorder"Metabolism. 49. 1145-1149 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K. Komatsu, S. Suzuki, T. Shimosegawa, J. I. Miyazaki, T. Toyota: "Cre-loxP-mediated bax gene activation reduces growth rate and increases sensivity to chemotherapeutic agents in human gastric cancer cells"Cancer Gene Ther. 7. 885-892 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] F. Okamura, A. Tashiro, A. Utumi, T. Imai, T. Suchi, D. Tamura, Y. Sato, S. Suzuki, M. Hongo: "Insulin resistance in patients with depression and its changes during the clinical course of depression : minimal model analysis"Metabolism. 49. 1255-1260 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y. Hinokio, Y. Horikawa, H. Furuta, N. J. Cox, N. Iwasaki, M. Honda, M. Ogata, Y. Iwamoto, G.I. Bell: "Beta-cell transcription factors and diabetes : no evidence for diabetes-associated mutations in the hepatocyte nuclear factor-3beta gene (HNF 3B) in Japanese patients with maturity-onset diabetes of the young"Diabetes. 49. 302-305 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A. Abderrahmani, J. C. Chevre, S. Otabe, M. Chikri, E. H. Hani, M. Vaxillaire, Y. Hinokio, Y. Horikawa, G. I. Bell, P. Froguel: "Genetic variation in the hepatocyte nuclear factor-3beta gene (HNF3B) does not contribute to maturity-onset diabetes of the young in French Caucasians"Diabetes. 49. 306-308 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hirai M.: "Variations in vitamin D-binding protein (group-specific component protein) are associated with"J Chin endocrinol Metab. 85. 1951-1953 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Masaki Chiba: "Tyrosice hydroxylase gene microsattellite"Metabolism. 49. 1145-1149 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Koga Komatsu: "Cre-Loxp-mediated bax gene activation"Cancer Gene Ther. 7. 885-892 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Okamma F: "Insulin resistance in patients eith depression"Metabolism. 49. 1255-1260 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Baier L.J.: "Mutations in the genes for hepatocyte nuclear"Diabetes Care. 23. 302-304 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Horikawa Y.: "Genetic variation in the gene encoding"Nature Genet. 26. 163-175 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hirai,M.: "Variations in Vitamin D-binding proteins are associated with footing plaoma insulin levels in Japanese…"J.Oin Endocrinol.Metab.. 85. 1951-1953 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hinokio,Y.: "Beta cell transcription factors and diabetes: nosuidence for diadetes-associated mutations"Diabetes . 49. 302-305 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Chiba: "Tyrosine hydroxylase gene microsatellite polymorphism associated with insalin resistance in depressive"Metabalism. 49. 1145-1149 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Komafsu K.: "Cre-loxP-mediated bax gene activation reduces growth rate and increasest sensitivity to chemotherapy."Cancer Gene Ther.. 7. 885-892 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Horikawa Y.: "Genetic variation in the gene encoding calpain10 is associated with type 2 diabetes mellitas."Nature Genetics. 26. 163-175 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Okamura,F.: "Insalin resistance in patients with depression"Metabolism. 49. 1255-1260 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 鈴木進: "糖尿病キーワード第2版"日本医学出版. 133 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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