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The medicine that functions to maintain the redox state might to the pathological conditions of insulin resistance

Research Project

Project/Area Number 15590062
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionGifu Pharmaceutical University

Principal Investigator

ADACHI Tetsuo  Gifu Pharmaceutical University, Laboratory of Clinical Pharmaceutics, Professor, 薬学部, 教授 (40137063)

Co-Investigator(Kenkyū-buntansha) HARA Hirokazu  Gifu Pharmaceutical University, Laboratory of Clinical Pharmaceutics, Research assistant, 薬学部, 研究助手 (30305495)
INOUE Minoru  Showa University, Fujigaoka Hospital, Division of Endocrinology and Department of Internal Medicine, Associate professor, 医学部, 講師 (30306998)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2003: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsSuperoxide dismutase / Insulin resistance / Oxygen stress / Tumor necrosis factor-α / Transcription factors / Atherosclerosis / Pioglitazone / Extracellular-superoxide dismutase
Research Abstract

Extracellular-superoxide dismutase (EC-SOD) is a secretory glycoprotein located in blood vessel walls at high levels and may be important in the antioxidant capability of vascular walls. The aim of this study was to assess plasma levels of EC-SOD and to evaluate the relationship of the EC-SOD level with insulin resistance in type 2 diabetic patients. We determined plasma EC-SOD in 122 patients and found for the first time that the EC-SOD level was strongly and positively related to adiponectin, and significantly and inversely related to fasting plasma glucose, body mass index (BMI) and homeostasis model assessment-insulin resistance index (HOMA-R). Administration of pioglitazone to 19 diabetic patients significantly increased the plasma levels of EC-SOD and adiponectin, while it decreased tumor necrosis factor-α (TNF-α). The present observations suggest that factors related to the pathogenesis of insulin resistance play an important role in the regulation of the plasma EC-SOD concentration.
Expression of EC-SOD is known to be regulated by numerous substances such as cytokines and vasoactive factors. Transcription factors such as CCAAT/enhancer-binding proteins (C/EBPs) and peroxisome proliferator-activated receptors (PPARs) are known to regulate genes associated with insulin resistance. We found that a C/EBPβ enhancer, prolactin, significantly induced the EC-SOD mRNA and protein levels in cultured fibroblast cell lines, but PPARγ ligands, pioglitazone and other thiazolidinedione agents did not. Deletion analysis of the EC-SOD promoter-luciferase construct showed that an important element responsible for prolactin is located between -242 and -178 in the promoter region of the EC-SOD gene in which a known C/EBPβ-binding site is located. Increasing the EC-SOD expression by treatment with ligands of transcription factors might be one approach to ameliorate the pathological conditions of insulin resistance.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (47 results)

All 2005 2004 2003 Other

All Journal Article (37 results) Book (4 results) Publications (6 results)

  • [Journal Article] 培養メサンギウム細胞の産生するExtracellular Superoxide Dismutase(EC-SOD)と細胞外基質2005

    • Author(s)
      山田 晴生 ら
    • Journal Title

      日本腎臓学会誌 47

      Pages: 32-37

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression of allograft inflammatory factor-1 in human eutopic endometrium and endometriosis : possible association with progression of endometriosis2005

    • Author(s)
      H.Koshiba, et al.
    • Journal Title

      J.Clin.Endocrinol.Metab. 90

      Pages: 529-537

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Extracellular superoxide dismutase overexpression reduced cuff-induced arterial neointimal formation2005

    • Author(s)
      K.Ozumi, et al.
    • Journal Title

      Atherosclerosis (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Experimental hyperhomocysteinemia impairs coronary flow velocity reserve2005

    • Author(s)
      K.Yamashita, et al.
    • Journal Title

      Int.J.Cardiology (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Extracellular-superoxide dismutase production in mesangial cell growing in extracellular matrix2005

    • Author(s)
      Yamada, H. et al.
    • Journal Title

      Jpn. J. Nephrol. 47

      Pages: 32-37

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression of allograft inflammatory factor-1 in human eutopic endometrium and endometriosis: possible association with progression of endometriosis2005

    • Author(s)
      Koshiba, H. et al.
    • Journal Title

      J. Clin. Endocrinol. Metab. 90

      Pages: 529-537

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 培養メサンギウム細胞の産生するExtracellular Superoxide Dismutase (EC-SOD)と細胞外基質2005

    • Author(s)
      山田 晴生 ら
    • Journal Title

      日本腎臓学会誌 47

      Pages: 32-37

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Upregulation of vascular extracellular superoxide dismutase in patients with acute coronary syndromes2004

    • Author(s)
      M.Horiuchi, et al.
    • Journal Title

      Arterioscler.Thromb.Vasc.Biol. 24

      Pages: 106-111

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Relationship of plasma extracellular-superoxide dismutase level with insulin resistance in type 2 diabetic patients.2004

    • Author(s)
      T.Adachi, et al.
    • Journal Title

      J.Endocrinol. 181

      Pages: 413-417

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Effects of PPARγ ligands and C/EBPβ enhancer on expression of extracellular-superoxide dismutase2004

    • Author(s)
      T.Adachi, et al.
    • Journal Title

      Redox Report 9

      Pages: 207-212

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] c-Jun N-terminal kinase modulates 1,25-dihydroxyvitamin D_3-induced cytochrome P450 3A4 gene expression2004

    • Author(s)
      Y.Yasunami, et al.
    • Journal Title

      Drug Metab.Dispos. 32

      Pages: 685-688

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Loss of CYP3A7 gene induction by 1,25-dihydroxyvitamin D_3 is caused by less binding of VDR to the proximal ER6 in CYP3A7 gene2004

    • Author(s)
      H.Hara, et al.
    • Journal Title

      Biochem.Biophys.Res.Commun. 321

      Pages: 909-915

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Hyperhomocysteinemia is associated with human coronary atherosclerosis through the reduction of the ratio of endothelium-bound to basal extracellular superoxide dismutase ratio2004

    • Author(s)
      S.Nihei, et al.
    • Journal Title

      Circulation J 68

      Pages: 822-828

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] The relationship between exercise-induced oxidative stress and the menstrual cycle2004

    • Author(s)
      M.H.Joo, et al.
    • Journal Title

      Eur.J.Appl.Physiol. 93

      Pages: 82-86

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] 骨芽細胞・破骨細胞のin vitroでの再現と活性酸素の関与2004

    • Author(s)
      山田 晴生 ら
    • Journal Title

      臨床透析 20

      Pages: 541-546

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Upregulation of vascular extracellular superoxide dismutase in patients with acute coronary syndromes2004

    • Author(s)
      Horiuchi, M. et al.
    • Journal Title

      Arterioscler. Thromb. Vasc. Biol. 24

      Pages: 106-111

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Relationship of plasma extracellular-superoxide dismutase level with insulin resistance in type 2 diabetic patients2004

    • Author(s)
      Adachi, T. et al.
    • Journal Title

      J. Endocrinol 181

      Pages: 412-417

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effects of PPARγ ligands and C/EBPβ enhancer on expression of extracellular-superoxide dismutase2004

    • Author(s)
      Adachi, T. et al.
    • Journal Title

      Redox Report 9

      Pages: 207-212

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] c-Jun N-terminal kinase modulates 1,25-dihydroxyvitamin D_3-induced cytochrome P450 3A4 gene expression2004

    • Author(s)
      Yasunami, Y. et al.
    • Journal Title

      Drug Metab. Dipos. 32

      Pages: 685-688

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Loss of CYP3A7 gene induction by 1,25-dihydroxyvitamin D_3 is caused by less binding of VDR to the proximal ER6 in CYP3A7 gene2004

    • Author(s)
      Hara, H. et al.
    • Journal Title

      Biochem. Biophys. Res. Commun. 321

      Pages: 909-915

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Hyperhomocysteinemia is associated with human coronary atherosclerosis through the reduction of the ratio of endothelium-bound to basal extracellular superoxide dismutase ratio2004

    • Author(s)
      Nihei, S. et al.
    • Journal Title

      Circulation J. 68

      Pages: 822-828

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The relationship between exercise-induced oxidative stress and the menstrual cycle2004

    • Author(s)
      Joo, M.H.et al.
    • Journal Title

      Eur. J. Appl. Physiol. 93

      Pages: 82-86

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Possible mimics of osteoblast and osteoclast function associated with the reactive oxygen and extracellular superoxide dismutase in vitro2004

    • Author(s)
      Yamada, H. et al.
    • Journal Title

      Clinical Hemodialysis 20

      Pages: 541-546

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression of extracellular superoxide dismutase in glomerular mesangial cells by predonisolone2004

    • Author(s)
      Yamada, H. et al.
    • Journal Title

      Kidney and Free Radical 7

      Pages: 26-29

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Possible mimics of osteoblast and osteoclast function associated with the reactive oxygen2004

    • Author(s)
      Yamada, H. et al.
    • Journal Title

      Kidney and Free Radical 5

      Pages: 112-115

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Serum extracellular superoxide dismutase in patients with type 2 diabetes. Relationship to the development of micro- and macro-vascular complications.2003

    • Author(s)
      F.Kimura, et al.
    • Journal Title

      Diabetes Care 26

      Pages: 1246-1250

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Blood extracellular superoxide dismutase (EC-SOD) levels in hemodialysis patients pre- and post-hemodialysis and its association with lipoprotein lipase mass and free fatty acid2003

    • Author(s)
      H.Shimomura, et al.
    • Journal Title

      Clin.Chim.Acta 328

      Pages: 113-119

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 糖尿病患者群における血漿ヒト脳性ナトリウム利尿ペプチド(BNP)レベルとアルブミン尿排泄指数(AEI),Extracellular superoxide dismutase(EC-SOD)との関連性について2003

    • Author(s)
      前畑 英介 ら
    • Journal Title

      生物試料分析 26

      Pages: 169-174

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 糖尿病性血管障害と酸化ストレス-EC-SODからの知見-2003

    • Author(s)
      足立 哲夫 ら
    • Journal Title

      生物試料分析 26

      Pages: 137-144

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 硝子体の病態生理,網膜硝子体疾患の分子レベルにおける病態解明2003

    • Author(s)
      池田 恒彦 ら
    • Journal Title

      日本眼科学会雑誌 107

      Pages: 785-812

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Serum extracellular superoxide dismutase in patients with type 2 diabetes. Relationship to the development of micro- and macro-vascular complications2003

    • Author(s)
      Kimura, F. et al.
    • Journal Title

      Diabetes Care 26

      Pages: 1246-1250

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Blood extracellular superoxide dismutase (EC-SOD) levels in hemodialysis patients pre- and post-hemodialysis and its association with lipoprotein lipase mass and free fatty acid2003

    • Author(s)
      Shimomura, H. et al.
    • Journal Title

      Clin. Chim. Acta 328

      Pages: 113-119

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Plasma levels of human brain natriuretic peptide (BNP) in diabetics: Its correlations with the albumin excretion index (AEI) and extracellular (EC) superoxide dismutase (SOD)2003

    • Author(s)
      Maehata, E. et al.
    • Journal Title

      Anal. Clin. Specimen 26

      Pages: 169-174

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Implications of reactive oxygen species in diabetic vascular damage -Approach with EC-SOD-2003

    • Author(s)
      Adachi, T. et al.
    • Journal Title

      Anal. Clin. Specimen 26

      Pages: 137-144

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The pathogenesis of vitreoretinal diseases from the standpoint of molecular biology2003

    • Author(s)
      Ikeda, T. et al.
    • Journal Title

      Jpn. J. Ophthalmology 107

      Pages: 785-812

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Extracellular superoxide dismutase overexpression reduced cuff-induced arterial neointimal formation

    • Author(s)
      Ozumi, K. et al.
    • Journal Title

      Atherosclerosis (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Experimental hyperhomocysteinemia impairs coronary flow velocity reserve

    • Author(s)
      Yamashita, K. et al.
    • Journal Title

      Int. J. Cardiology (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] 腎とフリーラジカル 第7集-1(松澤直輝, 青柳一正)2004

    • Author(s)
      山田 晴生 ら
    • Total Pages
      4
    • Publisher
      東京医学社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] 腎とフリーラジカル第7集-2(松澤直輝, 青柳一正)2004

    • Author(s)
      山田 晴生 ら
    • Total Pages
      4
    • Publisher
      東京医学社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] 腎とフリーラジカル 第7集-12004

    • Author(s)
      山田 晴生 ら
    • Total Pages
      4
    • Publisher
      松澤直輝, 青柳一正(東京医学社)
    • Related Report
      2004 Annual Research Report
  • [Book] 腎とフリーラジカル 第7集-22004

    • Author(s)
      山田 晴生 ら
    • Total Pages
      4
    • Publisher
      松澤直輝, 青柳一正(東京医学社)
    • Related Report
      2004 Annual Research Report
  • [Publications] F.Kimura, et al.: "Serum extracellular superoxide dismutase in patients with type 2 diabetes. Relationship to the development of micro- and macro-vascular complications."Diabetes Care. 26. 1246-1250 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] H.Shimomura, et al.: "Blood extracellular superoxide dismutase(EC-SOD) levels in hemodialysis patients pre- and post-hemodialysis and its association with lipoprotein lipase mass and free fatty acid"Clin.Chim.Acta. 328. 113-119 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 前畑 英介ら: "糖尿病患者群における血漿ヒト脳性ナトリウム利尿ペプチド(BNP)レベルとアルブミン尿排泄指数(AEI), Extracellular superoxide dismutase(EC-SOD)との関連性について"生物試料分析. 26. 169-174 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 足立 哲夫ら: "糖尿病性血管障害と酸化ストレス-EC-SODからの知見-"生物試料分析. 26. 137-144 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] M.Horiushi, et al.: "Upregulation of vascular extracellular superoxide dismutase in patients with acute coronary syndromes"Arterioscler.Thromb.Vasc.Biol.. 24. 106-111 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] T.Adachi, et al.: "Regulation of extracellular-superoxide dismutase in the pathogenesis of insulin resistance"J.Endocrinol.. (in press). (2004)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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