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STUDY OF ABNORMAL GLUCOSE METABOLISM ASSOCIATED WITH AGEING AND ESTABLISHMENT FOR AN ANIMAL MODEL OF NIDDM

Research Project

Project/Area Number 09671022
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 InstitutionGUNMA UNIVERSITY

Principal Investigator

UTSUGI Toshihiro  GUNMA UNIVERSITY, 2ND INTERNAL MEDICINE, 医学部, 教務員 (10282386)

Co-Investigator(Kenkyū-buntansha) NAGAI Ryozo  GUNMA UNIVERSITY, 2ND INTERNAL MEDICINE, PROFESSOR, 医学部, 教授 (60207975)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1997: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsAgeing / Ageing suppressing gene / klotho / Diabetes mellitus / Glucose transporter / Klotho
Research Abstract

1. Klotho gene expression in the new animal model for human ageing and study for insulin deficiency in this model
1) We have recently identified a novel gene, termed klotho (kl), which may suppress several ageing phenotypes. Defect of kl gene expression in the mouse results in a syndrome resembling human ageing, such as arteriosclerosis, skin atrophy, osteoporosis, and pulmonary emphysema. The klotho gene is expressed in the kidney, artery, and lung. The gene sequence was 40% similarity with β-glucosidase. The gene expression in the kidney was decreased-in model rats for hypertension and diabetes mellitus. As the dysfunction of endothelial cells were recovered after parabiosis experiment, we suggest that the klotho gene products can act as a fluid factor, such as hormones and cytokines.
2) To see whether mouse homozygote for the kl mutation (kl/kl) show abnormal glucose metabolism and insulin deficiency, OGTT was performed at 6-8 weeks of age. Blood glucose levels during OGTT in kl/kl mi … More ce were significantly lower than those in wild mice. Whereas, insulin content of the pancreas in kl/kl mice-was significantly lower compared to that of control mice. The decreased insulin production was also supported by Northern blot analysis that showed lower levels of insulin mRNA in kl/kl mice.
3) Histological findings showed that pancreatic β cells were selectively diminished, and α cells were slightly increased in number in the klotho mice. We could not find immunocytes in the islets of pancreas and apoptosis signals were not detectable, suggesting that the insulin deficiency could be due to direct effect by defect of kl gene expression in the klotho mouse.
These findings were published in Nature 1997, Biochem Biophys Res Comm 1998, and reported in several national and international meetings, such as Japan diabetes association, European association for study of the diabetes, and so on.
2. Establishment for the animal model for NIDDM
This study was initiated to see high calorie diet can induce NIDDM in mouse heterozygote for the kl mutation (kl/+) that has increased insulin sensitivity. So far, no animal developped NIDDM for one years.
3. Study for prevention of abnormal glucose metabolism using the purified klotho protein
Purification of klotho protein is now on-going. Once purified and prepared for administration in vivo, this study can performed. Less

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Oyama Y, Utugi T, Nagai R, et al: "Insulin production and insulin penstirity in the klotho mutant mouse"Diabetologia. 41. A393 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Matsumura Y, Nagai R, et al: "Identification of the human klotho gene and its two transcriptsencoding membrane and secseted klotho protain"Biochem Biopys Res Comm. 242. 626-630 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Aizawa H., Nagai R. et al: "Doun regulation of the klotho gene in the kidny under sustained clroulatory stress in rats"Biochem Biophys Res Comm. 249. 865-871 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Oyama Y, Utsugi T, Nagai r et al: "Inslin production and Insulin Sensitibity in the kloth mueant mane, the novel animal for human aging"Diabetes. 47. A393 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 宇津木敏浩、永井良三、他: "老化抑制遺伝子klotho欠損マウスにおける糖代謝とインスリン抵抗性の検討"日本臨床代謝学会記録. 35. 84-84 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 大山良雄、宇津木敏浩、永井良三、他: "老化抑制遺伝子(kloto)欠損マウスにおける糖代謝と膵内分泌機能の検討"Diabetes Frontier. 9. 363-364 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] OHYAMA Y, UTSUGI T, NAGAI R, ET AL: "INSULIN PRODUCTION AND INSULIN SENSITIVITY IN THE KLOTHO MUTANT MOUSE"DIABETOLOGIA. 41. A393 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] MATSUMURA Y, NAGAI R, ET AL: "IDENTIFICATION OF THE HUMAN KLOTHO GENE AND ITS TWO TRANSCRIPTS ENCODING MEMBRANE AND SECRETED KLOTHO PROTEIN"BIOCHEM BIOPHYS RES COMM. 242. 626-630 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] AIZAWA H, NAGAI R, ET AL: "DOWN REGULATION OF THE KLOTHO GENE IN THE KIDNEY UNDER SUSTAINED CIRCULATORY STRESS IN RATS"BIOCHEM BIOPHYS RES COMM. 249. 865-871 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] OHYAMA Y, UTSUGI T, NAGAI R, ET AL: "INSULIN PRODUCTION AND INSULIN SENSITIVITY IN THE KLOTHO MUTANT MOUSE, THE NOVEL ANIMAL FOR HUMAN AGEING"DIABETES. 47. A393 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] UTSUGI T, NAGAI R, ET AL: "ABNORMAL GLUCOSE METABOLISM AND INSULIN RESISTANCE IN THE KLOTHO MUTANT MOUSE"NIHON RINSHO TAISYA GAKKAI-SHI. 35(JAPANESE). 84 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] OHYAMA Y, UTSUGI T, NAGAI R, ET AL: "GLUCOSE METABOLISM AND PANCREATIC BETA CALL FUNCTION IN THE KLOTHO MUTANT MOUSE"DIABETES FRONTIER. 9(JAPANESE). 363-364 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ohyama Y,Utsugi T,Nagai R. et al: "Insulin production and insulin senstrivity in the Klotho mutant mouse." Diabetologia. 41. A393 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Matsumura Y,Nagai R. et al: "Identification of the human Klotho glne and its two transcripts encoding membrane and secutul Klotho procein." Biochem Biophys Res Comm. 242. 626-630 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Aizawa H. ,Nagai R. et al: "Doun regulation of the Kltho gene in the Kidney wndin sus taincd clrculatory seuss in rats." Biochem Biophys Res Comm. 249. 865-871 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ohyama Y,Utsugi T,Nagai R. et al: "Inslin produet in and Insulin Sinsitivity in the Kloth mueant mnne,the roul animal for human ageing" Diaheres. 47. A393 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 宇都木敏浩.永井良三 他: "老化抑制遺伝子Klotho欠損マウスにおける糖代謝とインスリン抵抗性の検討" 日本臨床代謝学会記録. 35. 84-84 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 大山良雄.宇都木敏浩.永井良三他: "老化抑制遺伝子(Klotho)欠損マウスにおける糖代謝と膵内分泌機能の検討" Diahetes Frontier. 9. 363-364 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kuro-o-M, Utsugi T., Nagai R., at al: "Mutation of the mouse Klotho gene leads to asyndrone resembling ageing" Nature. 390. 45-51 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 宇都木 敏浩: "動脈硬化と糖尿病の発症を共通に制御する老化遺伝子の解明" 成人病の研究. 16巻. 28-29 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 大山良雄, 宇都木 敏浩ら: "老化抑制遺伝子(Klotho)欠損マウスにおける糖代謝と脾分泌機能の検討" Diabetes Frontier. (予定). (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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