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1998 Fiscal Year Final Research Report Summary

Role of oxidative DNA damage in the pathogenesis of diabetic complications

Research Project

Project/Area Number 09671019
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内分泌・代謝学
Research InstitutionTohoku University

Principal Investigator

SUZUKI Susumu  Tohoku University, 3rd Dep Int Med, research associate, 医学部・附属病院, 助手 (70216399)

Co-Investigator(Kenkyū-buntansha) HINOKIO Yoshinori  Tohoku University, 3rd Dep Int Med, research associate, 医学部・附属病院, 助手 (10282071)
Project Period (FY) 1997 – 1998
KeywordsOxidative stress / 8-oxo-2'-deoxyguanosine / mitochondrial DNA / diabetic nephropathy / diabetic retinopathy / アポトーシス / DNA損傷
Research Abstract

Augmented oxidative stress induced by hyperglycemia may contribute to the pathogenesis of diabetic complications. Oxidative stress is known to increase the conversion of deoxyguanosine(dG) to 8-oxo, 2'-deoxyguanosine (8-oxodG) in DNA.To investigate the possible. contribution of oxidative DNA damage to the pathogenesis of diabetic complicfttions, we measured the 8-oxodGcontents in the urine and the blood mononuclear cells of type 2 diabetic patients.
The contents of 8-oxodG in the urine and the mononuclear cells of the type 2 diabetic patients were much higher than those of the control subjects. Urinary excretion of 8-oxodG was significantly correlated with the 8-oxodG content in the mononuclear cells (R=0.855, p<0.0001). The 8-oxodGcontents in the urine (R=0.783, p<0.0001) and mononuclear cells (R=0.796, p.<0.0001) were correlated with the hemoglobin A1c level. Urinary 8-oxodG excretion and the 8-oxodG content in the mononuclear cells were augmented in proportion to the severity of diabetic nephropathy as well as retinopathy. These data provide evidence that augmented oxidative DNA damage in diabetes is linked to diabetic complications.
This is the first report showing that the increase in 8-oxodG is proportional to the severity of diabetic complications. Oxidative DNA damage is speculated to contribute to the pathogenesis of diabetic complications. 8-oxodG in urine and mononuclear cells is a useful marker to evaluate oxidative DNA damage in diabetic patients.

  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Yoshinori Hinokio: "Oxidative DNA damage in Diabetes : tts association with diabetic complication." Diabetologia. (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Susumu Suzuki: "Oxidative DNA damage and its relationship to diabetic complication" Diabetis Res Oin Proct.(1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Susumu Suzuki: "The effects of coenzyme Q_<10> treatment on maternol-inherited diabetes mellitus with deafness and mitochondrial DNA mutation." Diabetologia. 41. 584-588 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Masashi Hirai: "Mitochondorial deoxyribonucleic acid 3256 C-T mutation in an Japanese family with on-insulin dependent diabetes mellitus." J Clin Endocrinol Metab. 83. 992-994 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Masashi Hirai: "Group-specific component protain denotype is associated with non-insulin dependent diabetis mellitus in Japan" Diabetologia. 41. 742-743 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshihiko Suzuki: "Diabetis associated with anovel 3264 mitochondorial tRNA Leu〓〓 mutation." Diabetes Care. 20. 1134-1140 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 豊田隆謙: "糖尿病キーワード" 日本医学出版, 119 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Hinokio, S.Suzuki, M.Hirai, M.Chiba, A.Hirai, T.Toyota: "Oxidative DNA Damage in Diabetes : Its Association with Diabetic Complications" Diabetologia. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Suzuki, Y.Hinokio, K.Komatu, M.Ohtomo, M.Onoda, S.Hirai, M.Hirai, A.Hirai, M.Chiba, S.Kasuga, H.Akai and T.Toyota: "Oxidative DNA damage and its relationship to diabetic complications." Diabetes Res Clin Pract. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] N.Matsuura, S.Suzuki, M.Hirai, Y.Yokota, K.Kazahari, M.Kazahari, T.Toyota, A.Okuno, S.Harada, N.Fukushima, A.Koike, Y.Itoh and T.Hotsubo.: "Mitochondrial gene mutations associated with childhood diabe-tes mellitus in Japanese." J Pediatric Endcrinol Metab. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Suzuki, Y.Hinokio, M.Ohtomo, M.Hirai, A.Hirai, M.Chiba, S.Kasuga, Y.Saitoh, H.Akai and T.Toyota.: "The Effects of coenzyme Q10 treatment on maternal-inherited diabetes mellitus with deafness and mitochondrial DNA 3243 (A to G) mutation." Diabetologia. 41. 584-588 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Hirai, S.Suzuki, M.Onoda, Y.Hinokio, A.Hirai, M.Ohtomo, M.Chiba, S.Kasuga, Y.Satoh, H.Akai, S.Miyabayashi and T.Toyota.: "Mitochon-drial deoxyribonucleic acid 3256C-T mutation in an Japanese family with noninsulin dependent diabetes mellitus." J Clin Endocrinol Metab. 83. 992-994 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Hirai, S.Suzuki, Y.Hinokio, M.Chiba, S.Kasuga, A.Hirai and T.Toyota.: "Group-specific component protein genotype is associated with non-insulin dependent diabetes mellitus in Japan." Diabetologia. 41. 742-743 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Horikawa, N.Iwasaki, M.Hara, H.Furuta, Y.Hinokio, B.Cockburn, T.Lindner, K.Yamagata, M.Ogata, O.Tomonaga, H.Kuroki, T.Kasahara, Y.Iwamoto and G.Bell.: "Mutation in hepatocyte nuclear factor-1beta gene (TCF2) associate with MODY" Nature Genet. 17. 384-385 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Suzuki, S.Suzuki, Y.Hinokio, M.Chiba, Y.Atsumim, K.Hosokawa, A.Shimada and K.Matsuoka.: "Diabetes associated with a novel 3264 mito-chondrial tRNALeu (UUR) mutation" Diabetes Care. 20. 1138-1140 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Suzuki, T.Muramatsu, M.Taniyama, Y.Goto, Y.Oka, S.Suzuki, K.Tsukuda, Y.Atsumi, I.Nonaka, K.Hosokawa, A.Shimada, T.Asahina and K.Matsuoka: "No assciation of ALDH2 genotype in MELAS" Diabetologia. 40. 1241-1242 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Ogata, T.Uchimura, Y.Iizuka, R.Murata, S.Suzuki, T.Toyota and N.Hikichi.: "Effect of Non-insulin depenent diabetes on cyclosporin a disposi-tion in Goto-Kakizaki (GK) rats." Biochem Pharm Bull. 20. 1026-1029 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Toyota, J.Satoh and S.Suzuki.: "Diabetic neuropathy." Internal Medicine. 36. 139-142 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Furuta, N.Iwasaki, N.Oda, Y.Hinokio, Y.Horikawa, K.Yamagata, N.Yano, J.Sugahiro, M.Ogata, H.Ohgawara, Y.Omori, Y.Iwamoto and G.Bell.: "Organization and partial sequence of the hepatocyte nuclear factor-4alpha/MODY1 gene and identification of a missense mutation, R127W,in a Japanese family with MODY" Diabetes. 46. 1652-1657 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] N.Iwasaki, N.Oda, M.Ogata, M.Hara, Y.Hinokio, Y.Oa, K.Yamagata, S.Kanematsu, H.Ohgawara, Y.Omori and G.Bell: "Mutations in the hepa-tocyte nuclear factor-1alpha/MODY3 gene in Japanese subjects with early or 1ate-onset NIDDM." Diabetes. 46. 1504-1508 (1997)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-12-08  

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