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Molecular mechanisms of the developments of Graves' disease and diabetes mellitus ; O_2 production-DNA damage and their signal transductions

Research Project

Project/Area Number 03807160
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field 内分泌・代謝学
Research InstitutionUniversity of the Ryukyus (1993)
Shinshu University (1991-1992)

Principal Investigator

TAKASU Nobuyuki  Department of Medicine, University of the Ryukyus, Professor, 医学部, 教授 (20020927)

Co-Investigator(Kenkyū-buntansha) 相沢 徹  信州大学, 医学部・附属病院, 講師 (90150896)
小宮 一郎  信州大学, 医学部, 講師 (50162061)
Project Period (FY) 1991 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1993: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1992: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1991: ¥1,200,000 (Direct Cost: ¥1,200,000)
KeywordsGraves' disease / diabetes mellitus / thyroid / pancreatic B cells / O_2 production / DNA fragmentation / signal transduction / autoimmune endocrine diseases
Research Abstract

There are many patients with Graves' disease and diabetes mellitus. Both Graves' disease and diabetes mellitus are autoimmune diseases. However, we do not know the molecular mechanisms of the developments of Graves' disease and diabetes mellitus. Thus we intended to reveal the molecular mechanisms of the developments of Graves' disease and diabetes mellitus, and found that O_2 production and consequent DNA fragmentation playd very important roles in the development of both diseases. We also studied the signal transduction systems of O_2 production and DNA fragmentation. We cultured thyroid cells and pancreatic islets and conducted many experiments.
We obtained a clear evidence for the molecular mechanism of the development of diabetes mellitus. Streptozotocin and alloxan exhibit the most potent diabetogenecity, and have been used for induction of experimental diabetes mellitus. DNA fragmentation plays an important role for the development of diabetes. Our in vitro and vivo experiments demonstrated that streptozotocin and alloxan stimulated H_2O_2 generation, which induced DNA fragmentation. Streptozotocin and alloxan induce diabetes through the following biochemical events ; streptozotocin and alloxan->H_2O_2 generation->DNA fragmentation->diabetes. As a signal transduction system, Ca plays an important role in streptozotocin and alloxan->H_2O_2 generation->DNA fragmentation->diabetes.

Report

(4 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • 1991 Annual Research Report
  • Research Products

    (41 results)

All Other

All Publications (41 results)

  • [Publications] F.Ishihara,M.Komatsu,T.Yamada.et al.: "Role of dehydroepiandrosterone and dehydroepiandrosterone sulfate for the maintenance of axillary hair in women" Horm Metab Res. 25. 34-36 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] I.Komiya,N.Takasu,T.Yamada,et al.: "Studies on the association of NIDDM in Japanese patients with hyperthyroid Graves' disease" Hormone Research. 38. 264-268 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] N.Takasu,T.Yamada,N.Ohara,I.Komiya: "Development of autoimmune thyroid dysfunction after bilateral adrenalectomy in a patient with Carney's complex and after removal of ACTH-producing pituitary adenoma in a patient with Cushing's disease" J Endocrinol Invest. 16. 697-702 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] M.Komatsu,N.Takasu,et al.: "Mastoparan-induced hormone release from the rat pancreatic islets." Endocrinology. 130. 221-228 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] N.Takasu,et al.: "Disappearance of thyrotropin-stimulation blocking antibody and spontaneous recovery from hypothyroidism." New Engl J Med. 326. 513-518 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] N.Takasu,et al.: "Requirements of follicle structure for thyroid hormone synthesis;cytoskeletons and iodine metabolism in polarized double layered,follicle-forming cells." Endocrinology. 131. 1143-1148 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] N.Takasu: "80 years of Hashimoto Disease(Reversible hypothyroidism)" Elsevier Science Publishes(Amsterdam), 155-160 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] N.Takasu: "80 years of Hashimoto Disease(Recovery from hypothyroidism and thyroid stimulation blocking antibodies)" Elsevier Science Publishes(Amsterdam), 695-697 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Takasu, N.et al.: "Alloxan-induced DNA strand breaks in pancreatic islets -evidence for H_2O_2 as an intermediate-." The Journal of Biological Chemistry. 266. 2112-2114 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Takasu, N.et al.: "Streptozocin- and alloxan-induced H_2O_2 generation and DNA fragmentation in pancreatic islets-H_2O_2 as mediator for DNA fragmentation-." Diabetes. 40. 1141-1145 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Takasu, N.et al.: "Interrelationship between insulin like growth factor I-induced activation of the Na'/H'-antiporter and intracellular Ca^<21>-mobilization in thyroid cells." Biochemical and Biophysical Research Communications. 177. 113-119 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Takasu, N.et al.: "Disappearance of thyrotropin-blocking antibodies and spontaneous recovery from hypothyroidism in autoimmune thyroiditis." New England Journal of Medicine. 326. 513-518 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Takasu, N.et al.: "Requirements of follicle structure for thyroid hormone synthesis ; cytoskeletons and iodine metabolism in polarized monolayr cells on collagen gel and in double layred, follicle-forming cells." Endocrinology. 131. 1143-1148 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Takasu, N.et al.: "Development of autoimmune thyroid dysfunction after bilateral adrenalectomy in a patient with Carney's complex and after removal of ACTH-producing pituitary adenoma in a patient with Cushing's desease." Journal of Endocrinological Investigation. 16. 691-702 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Komatsu, M., Takasu, N.et al.: "Mastoparan-induced hormone release from rat pancreatic islets." Endocrinology. 130. 221-228 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Komiya, I., Takasu, N.et al.: "Studies on the association of NIDDM in Japanese patients with hyperthyroid Graves' disease." Hormone Research. 38. 264-268 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ishihara, F., Takasu, N.et al.: "Role of dehydroepiandrosterone and dehydroepiandrosterone sulfate for the maintenance of axillary hair in women." Hormone and Metabolic Research. 25. 34-36 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Shirota, T., Takasu, N.et al.: "Primary hypothyroidism and multiple endocrine failure in association with hemochromatosis in a long-term hemodialysis patient." Clinical Nephrology. 38. 105-109 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ishihara, F., Takasu, N.et al.: "Role of adrenal androgens in the development of arteriosclerosis as judged by pulse wave velocity and calcification of the aorta." Cardiology. 80. 332-338 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Shigematsu, S., Takasu, N.et al.: "Differential effects of nifedipine on plasma atrial natriuretic peptide in normal subjects and hypertensive patients." Angiology. 43. 40-46 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Komatsu, M., Takasu, N.et al.: "Gradual delay in glucose-induced first phase insulin secretion by the pancreaticislets of 7 week-, 6 month, and 1 year-old rats." Journal of Gerontology. 46. B59-64 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Komiya, I., Takasu, N.et al.: "Inappropriate elevation of the aldosterone/plasma renin activity ratio in hypertensive patients with increase of 11-deoxycorticosterone and 18-hydroxy-11-deoxycorticosterone : a subtype of essential hypertension?" Cardiology. 78. 99-110 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] F.Ishihara,M.Komatsu,T.Yamada,et al.: "Role of dehydroepiandrosterone and dehydroepiandrosterone sulfate for the maintenance of axillary hair in women" Horm Metab Res. 25. 34-36 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] I.Komiya,N.Takasu,T.Yamade,et al.: "Studies on the association.of NIDDM in Japanese patients with hyperthyroid Graves′disease" Hormone Research. 38. 264-268 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] N.Takasu,T.Yamada,N.Ohara,I.Komiya: "Development of autoimmune thyroid dysfunction after bilateral adrenalectomy in a patient with Carney′s complex and after removal of ACTH-producing pituitary adenoma in a patient with Cushing′s disease" J Endocrinol Invest. 16. 697-702 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] N.Takasu T.Yamada: "80 years of Hashimoto Disease(Reversible hypothyroidism)" Elsevier Science Publishes(Amsterdam), 155-160 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] N.Takasu T.Yamada: "80 years of Hashimoto Disease(Recovery from hypothyroidism and thyroid stimulation blocking antibodies)" Elsevier Science Publishes(Amsterdam), 695-697 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Takasu N et al.: "Requirements of follicle structure for thyroid hormone synthesis;cytoskeletons and iodine metabolism in polarized monolayer cells on collagen gel and in double layered,follicle-forming cells." Endocrinology. 131. 1143-1148 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Komiya I,Takasu N: "Studies of the association of NIDDM in patients with hyperthyroid Graves′ disease" Hormone Research.

    • Related Report
      1992 Annual Research Report
  • [Publications] Takasu N et al.: "Disappearance of TSH-stimulation blocking antibody and spontaneous recovery from hypothyroidism." New Engl J Med. 326. 223-230 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Takasu N et al.: "Streptozotocin- and alloxan-induced H_2O_2 generation and DNA fragmentation in pancreatic islets." Diabetes. 40. 1141-1145 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] Takasu N et al.: "Alloxan-induced DNA strand breaks in pancreatic isletsevidence for H_2O_2 as an intermediate." J Biol Chem. 266. 2112-2114 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] Takasu N et al.: "Interrelationship between insulin-like growth factorinduced activation of the Na^+/H^+-antiporter and intracellular Cat^<2+>-mobilization in thyroid cells." Biochem Biophys Res Commun. 177. 113-119 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] 高須 信行: "日本生化学会編.新生化学実験講座9.ホルモンII 甲状腺細胞の分化・増殖の情報伝達機構研究法" 東京化学同人,東京, 41-49 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 高須 信行: "生物薬科実験講座9.ホルモン 甲状腺" 朝倉書店,東京, (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Takasu N et al.: "Alloxanーinduced DNA strand breaks in pancreatic isletsevidence for H_2O_2 as an intermediate." J.Biol Chem. 266. 2112-2114 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Takasu N et al.: "Interrelationship between insulinーlike growth factorーinduced activation of the Na^+/H^+-antiporter and intracellular Cat^<2+>-mobilization in thyroid cells." Biochem Biophys Res Commun. 177. 113-119 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Takasu N et al.: "Streptozotocinーand alloxanーinduced H_2O_2 generation and DNA fragmentation in pancreatic islets." Diabetes. 40. 1141-1145 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Takasu N et al.: "Disappearance of TSHーstimulation blocking antibody and spontaneous recovery from hypothyroidism." New Engl J Med. 326. 223-230 (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Komiya I,Takasu N: "Inappropriate elevation of the aldosterone/plasma renin activity ratio in hypertensive patients with increases of 11ーdeoxycorticosterone and 18ーhydroxyー11ーdeoxycorticosterone:a subtype of essential hypertension." Cardiology. 78. 99-110 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Komatsu M,Takasu N: "Gradual delay in glucoseーinduced first phase insulin secretion by pancreatic islets of 7weekー,6monthsー,and 1yearーold rats." Journal of Gerontology. 46. B59-64 (1991)

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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