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Study on the pathogenetic roles of mutation of mitochondrial DNA at position 3243 on diabetes mellitus

Research Project

Project/Area Number 06671064
Research Category

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

Allocation TypeSingle-year Grants
Research Field 内分泌・代謝学
Research InstitutionOkinaka Memorial institute for Medical Research

Principal Investigator

KOBAYASHI Tetsuro  Research associate Okinaka Memorial Institute for Medical Research, 研究員 (30113442)

Co-Investigator(Kenkyū-buntansha) NAKANISHI Koji  Research associate Okinaka Memorial Institute for Medical Research, 研究員 (80211423)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1994: ¥1,400,000 (Direct Cost: ¥1,400,000)
Keywordsmitochondrial DNA / diabetes mellitus / mitochondrial enzyme / beta cell / amyloid / ミトコンドリア遺伝子異常 / HLA / 膵島細胞抗体
Research Abstract

In situ characterization of the islet in diabetics with mitochondrial DNA mutation at 3243 base pair (mt DNA 3243 mutation) was carried out.
In the present study, the islets in the diabetic patients with mt DNA 3243 mutation were examined in terms of beta cell volume and mitochondrial enzyme activities.
Thirty-four pancreata, including 10 pancreata from NIDDM patients, 14 pancreata from IDDM patients, and 10 non-diabetics, were composed of the subjects. Cytochrome c oxidase (COX) and succinate dehydrogenase (SDH) activities of the pancreas were stained histochemically.
mtDNA 3243 was detected in only 1 of 34 pancreata. Pancreatic beta cell volume in this case was decrease to 0.22 g. Fifty-two islets were examined in a section stained for mitochondrial enzymes including COX and SDH.All islets of an IDDM case with mtDNA 3243 mutation lacked COX enzyme activity, while other islets from 13 IDDM patients, 10 NIDDM patients and 10 non-diabetics had positive COX activity. All islets in the case with mtDNA 3243 mutation examined for SDH activity showed positive enzyme activity, while there were weak activity in the islet for SDH in IDDM,NIDDM and non-diabetics, who did not have the mutation. Pancreatic amyloid was demonstrated in a case with mtDNA 3243.
In conclusion, markedly decreased beta cell volume with diminished activity of mitochondrial DNA encoded-enzyme (COX) was demonstrated in an IDDM patients with mtDNA 3243 mutation.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (6 results)

All Other

All Publications (6 results)

  • [Publications] 小林 哲郎: "ミトコンドリア遺伝子異常とslowly progressive IDDM" 臨床検査. 38. 1329-1330 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tetsurou Kobayashi: "Association between HLA and Islet Cell Antibodies in Diabetic Patients with a Mitochondrial DNA Mutation at Base Pair 3243" Diabetologia. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] "Association between HLA and Islet Cell Antibodies in Diabetic Patients with a Mitochondrial DNA Mutation at Base Pair 3243" Daiabetologia. (in press). (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] "In Situ Characterization of Islet in Diabetes with Mitochondrial DNA Mutation at 3243 base pair" (Submitted).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tetsurou Kobayashi: "Association between HLA and Islet Cell Antibodies in Diabetic Patients with a Mitochondrial DNA Mutation at Base Pair 3243" Diabetologia,. (in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 小林,哲郎: "ミトコンドリア遺伝子異常とslowly progressive IDDM" 臨床検査. 38. 1329-1330 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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