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mechanism of insulin autoantibody production for pathogenesis of pancreatic beta cell destruction and hyperplasia

Research Project

Project/Area Number 13670478
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内科学一般
Research InstitutionTokyo Women's Medical University

Principal Investigator

UCHIGATA Yasuko  TWMU, Dept.of Medicine, Associate Prof., 医学部, 助教授 (50193884)

Co-Investigator(Kenkyū-buntansha) IWAMOTO Yasuhiko  TWMU, Dept.of Medicine, Professor, 医学部, 教授・所長 (60143434)
三浦 順之助  東京女子医科大学, 医学部, 助手 (90297515)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsInsulin autoantibody / Insulin autoimmune syndrome / Type 1 diabetes / Scatchard analysis / Insulin antibody
Research Abstract

Both of insulin autoimmune syndrome (IAS) and type 1 diabetes are characterized by insulin autoantibody. On the other hand, insulin antibody or anti-insulin antibody is a antibody against insulin which is injected subcutaneously. The insulin antibody and the insulin autoantibody have both an ability to bind insulin in human serum. Since reported by Hirata in 1970, we collected 244 patient record with insulin autoimmune syndrome (IAS) in Japan until 1997, which showed a development of averaged 9 patients with IAS per year. We collected 11 patients with IAS from 1998 to 1999, and collected 19 patients with IAS from 2000 to 2003. There was no increase of the development of IAS. Total of 274 patients with insulin autoimmune syndrome were collected in the end of 2003. Thirty-eight % of them was treated with sulfhydroxy compounds such as Methimazole, Thiola and Tathione before the development of IAS. According to the incidence of IAS, there was no increase year by year. Some of the patients had postprandial hyperglycemia after the development of IAS. the outcome of glucose tolerance test (GTT) was collected. Among them who were performed GTT, 59% had diabetic pattern, 38% had IGT pattern. It suggests that approximately 90% showed abnormal glucose metabolism. The characterization of the insulin autoantibody was done by Scatchard analysis using 125 I-human insulin. A major part of the insulin autoantibody was a high affinity (k1)-low capacity (b1) site, the site was compared with that of insulin antibody which were found in insulin-treated diabetic patients. The k1 and b1 were more than 1x10^8 L/mol and around 1 or less than 1x10^8 mol/L, respectively in insulin-treated diabetic patients, whereas those were less than 1x10^8 L/mol and more than 1x10^8 mol/L, respectively in the patients with IAS. There was a significant difference (p<0.001).

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Hara K, Tobe K, Uchigata Y, et al.: "Antibody-mediated insulin resistance treated with cessation of insulin administration"Internal Medicine. 392. 143-145 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Cavaco B, Uchigata Y et al.: "Hypoglycemia due to the insulin autoinmine syndrome : Repot of two cases with・・・・"Eur J Endocrinology. 145. 311-316 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 坂本啓子, 丸山道彦, 内潟安子: "インスリン抗体が血糖不安定の原因と考えられた1型糖尿病の1例"糖尿病. 45. 471-476 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 稲葉利敏, 六角久美子, 内潟安子ら: "Methimazole開始4年後に診断されたインスリン自己免疫症候群の1例"糖尿病. 46. 787-790 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 内潟安子: "看護のための最新医学講座 第8巻 インスリン自己免疫症候群"中山書店(東京). 286-292 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hara T, Tobe K, Uchigata Y, et al.: "Antibody-mediated insulin resistance treated with cessation of insulin administration"Internal Medicine. 392. 143-145 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Cabaco B, Uchigata Y, Porto T, et al.: "Hypoglycemia due to the insulin autoimmune syndrome ; Report of two cases with characterization of HLA alleles and insulin autoantibody"Eur J Endocrinology. 145. 311-316 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 阪本敬子, 丸山道彦, 鶴岡明, 内潟安子: "インスリン抗体が血糖不安定の原因と考えられた1型糖尿病の1例"糖尿病. 47(7). 471-476 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 高池浩子, 内潟安子: "高感度C-ペプチドIRMA法と従来のC-ペプチド測定2キットとの検討"糖尿病. 45(9). 653-658 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kawabata Y, Ikegami H, Uchigata Y, et al.: "Asian specific HLA haplotypes reveal heterogeneity to the contribution of HLA-DR and -DQ haplotypes"Diabetes. 51. 545-551 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Cavaco B, Uchigata Y.et al: "Hypoglycemia due to the insulin auto imme synarome : report of two cases with....."Eur J Endocrinol. 145. 311-316 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 内潟安子: "インスリン自己免疫症候群と糖尿病"内分泌・糖尿病科. 13(6). 610-613 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 内潟安子: "インスリン自己免疫症候群、看護のための最新医学講座8巻"中山書店(東京). 286-292 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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