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Studies on orally active antidiabetic vanadium complexes with low toxicity and long-term action

Research Project

Project/Area Number 08457622
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 医薬分子機能学
Research InstitutionKyoto Pharmaceutical University

Principal Investigator

SAKURAI Hiromu  Kyoto Pharm.Univ., Dep.Anal.& Bioinorg.Chem., Prof., 薬学部, 教授 (30065916)

Co-Investigator(Kenkyū-buntansha) OKA Shigenori  Kyoto Pharm.Univ., Dep.Anal.& Bioinorg.Chem., Res.Assist., 薬学部, 助手 (10268097)
YASUI Hiroyuki  Kyoto Pharm.Univ., Dep.Anal.& Bioinorg.Chem., Res.Assist., 薬学部, 助手 (20278443)
TAWA Riich  Kyoto Pharm.Univ., Dep.Anal.& Bioinorg.Chem., Lec., 薬学部, 講師 (80142587)
KANAMORI Kan  Toyama Univ., Fac.Sci., Prof., 理学部, 教授 (00019001)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥7,300,000 (Direct Cost: ¥7,300,000)
Fiscal Year 1997: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1996: ¥5,600,000 (Direct Cost: ¥5,600,000)
Keywordsvanadium / vanadyl complex / diabetes / insulin-like action / nitric oxide / IDDM / NIDDM
Research Abstract

We studied on development of orally active antidiabetic vanadyl complexes with low toxicity and long-term action to know the structure of the complex-activity relationship. Research was performed in the following steps. (1) Preparation of vanadyl complexes with different coordination modes and analysis of the structure. (2) In vitro evaluation of the complex using rat adipocytes in terms of suppression of free fatty acids and (3) in vivo evaluation of the possible complex, which was given to streptozotocin (STZ)-induced insulin-dependent diabetes mellitus (IDDM) rats or none-insulin-dependent diabetes mellitus (NIDDM) mice by ip injection or oral administration.
From the results for 2 years, we found that a vanadyl-picolinate complex with vo (v_2o_2) coordination mode has a good blood glucose normalizing effect on oral administration. Then we extended our work to find better complexes and found vanadyl-6-methyl-picolinate complex with low toxicity and long-term action when administered orally. The action mechanism of the complex was also analyzed in terms of vanadium organ distribution and pharmacokinetics. Interestingly, the complex was found to be effective on NIDDM mice when given by ip injection or oral administration. On the other hand, vanadium was found to be effective on the protection of development of STZ-induced diabetes. On the basis of the results, vanadium compounds were found to be effective to treat both IDDM and NIDDM in experimental animals as well as to protect the development of IDDM.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] 桜井 弘: "Vanadyl ion suppresses nitric oxide production from peritoneal macrophages of streptozotocin-induced diabetic mice." Biochem.Biophys.Res.Commun.226. 506-511 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 桜井 弘: "Orally active and long-term acting insulin-mimetic varadyl complex:Bis(picolirato)oxo-varadium(IV)" Biochem.Biophys.Res.Commun.214. 1095-1101 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 桜井 弘: "Mechanism on insulin-like action of vanadyl sulfate:Studies on interaction between rat adipolytes and vanadium" Biol.Pharm.Bull.15. 719-725 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 桜井 弘: "Syntheses,structures,and insulin-like activities of two vanadyl complexes;[VO(GeG)(H_2O)] and [VO(MeM)(H_2O)]" Chem.Lett.1998. 9-10 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 桜井 弘: "Insulin-mimetic vanadyl-dithiocarbamate complexes." Inorg.Chim.Acta.(印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 桜井 弘: "Long-term acting and orally active vanadyl-methyl picolinate complex with hypoglycemic activity in streptozotocin-induced dinbetic rats" J.Clin.Blochem.Nutr.(印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 桜井 弘: "バイオサイエンスESR(1),(2)" 廣川書店, 520 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 桜井 弘: "元素IIIの新知識" 講談社, 431 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hiromu Sakurai: "Vanadylion suppresses nitric oxide production from peritoneal macrophages of streptozotocin-induced diabetic mice." Biochem.Biophys.Res.Commun.226. 506-511 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hiromu Sakurai: "Orally active and long-term acting insulin-mimetic vanadyl complex : Bis (picolinato) oxo-vanadium (IV)." Biochem.Biophys.Res.Commun.214. 1095-1101 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hiromu Sakurai: "Mechanism on insulin-like action of vanadyl sulfate : Studies on interaction between rat adipocytes and vanadium compounds." Biol.Pharm.Bull.18. 719-725 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hiromu Sakurai: "Syntheses, structures, and insulin-like activities of two vanadyl complexes : [VO (GeG) (H_2O)] and [VO (MeM) (H_2O)]" Chem.Lett.1998. 9-10 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hiromu Sakurai: "Insulin-mimetic vanadyl-dithiocarbamate complexes." Inorg.Chim.Acta.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hiromu Sakurai: "Long-term acting and orally active vanadyl-methyl picolinate complex with hypoglycemic activity in streptozotocin-induced diabetic rats." J.Clin.Biochem.Nutr.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hiromu Sakurai: Bioscience ESR (1), (2). Hirokawa Schoten, (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hiromu Sakurai: New dictionary of elements 111. Kohdansya, (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 桜井 弘: "Vanadyl ion suppresses nitric oxide production from peritoneal macrophages of streptozotocin-induced diabetic mice." Biochem.Biophys Res.Commun.226. 506-511 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 桜井 弘: "Orally active and long-term acting insulin-mimetic vanadyl complex:Bis(picolinato) oxo-vanadium (IV)" Biochem.Biophys Res.Commun.214. 1095-1101 (1995)

    • Related Report
      1997 Annual Research Report
  • [Publications] 桜井 弘: "Mechanism on insulin-like action of vanadyl sulfate:Studies on interaction between rat adipocytes and vanadium compounds." Biol. Pharm. Bull.18. 719-725 (1995)

    • Related Report
      1997 Annual Research Report
  • [Publications] 桜井 弘: "Syntheses, Structures,and Insulin-like Activities of Two Vanadyl Complexes;[VO(GeG)(H_2O)]" Chem. Lett.1998. 9-10 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 桜井 弘: "Insulin-mimetic vanadyl-dithiocarbamate complexes." Inorg. Chim. Acta.(印刷中).

    • Related Report
      1997 Annual Research Report
  • [Publications] 桜井 弘: "Long-term acting and orally active vanadyl-methyl picolinate complex with hypoglycemic activity in streptozotocin-induced diabetic rats." J. Clin. Biochem. Nutr.(印刷中).

    • Related Report
      1997 Annual Research Report
  • [Publications] 桜井 弘: "バイオサイエンスESR(1),(2)" 廣川書店, 520 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 桜井 弘: "元素IIIの新知識" 講談社, 431 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 桜井弘: "糖尿病治療薬としてのバナジウム錯体" 現代化学. 1996(7). 14-20 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 桜井弘: "Antidiabetic action of vanadiuim complexes in animals : Blood glucose normalizing effect,organ distribution of vanadium" Vanadium in the environment,parts I & II. (印刷中). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 桜井弘: "Vanadylion suppresses nitric oxide production from peritoneae macrophages of streptozotocin-induced diabetic mice" Biochem.Biophys.Res.Commun.226. 506-511 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 桜井弘: "Pharmacohinetic analysis of paramagnetic species by in vivo BCM (Blood Circulation Monitoring) -ESR method" 磁気共鳴と医学. 8. 55-58 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 桜井弘: "バイオサイエンスESR(1)" 廣川書店, 266 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 桜井弘: "バイオサイエンスESR(2)" 廣川書店, 254 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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