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The approach for pathogenic mechanism of Type 1 diabetes using transgenic mice expressing TNFalpha selectively in pancreatic beta cells

Research Project

Project/Area Number 26350897
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Applied health science
Research InstitutionOita University

Principal Investigator

Kakuma Tetsuya  大分大学, 保健管理センター, 准教授 (80343359)

Co-Investigator(Kenkyū-buntansha) 正木 孝幸  大分大学, 医学部, 講師 (00423715)
後藤 孔郎  大分大学, 医学部, 助教 (10457624)
柴田 洋孝  大分大学, 医学部, 教授 (20245484)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords膵β細胞特異的TNFα過剰発現マウス / 糖尿病抵抗性 / 肥満抵抗性 / 脂肪肝抵抗性 / 機能的グルカゴン低下 / 糖代謝 / インスリン / グルカゴン / 高脂肪食負荷 / 高ショ糖負荷 / 加齢負荷 / ソマトスタチン / TNFα / AVP
Outline of Final Research Achievements

Transgenic mice expressing TNFα selectively in pancreatic βcells developed a severe insulitis, however, apparently resulting in positive glucose metabolism with relatively favorable insulin secretion against over-nutrition. Blood TNFα levels had no induction in transgenic mice because the line with low copy number of TNFα transgene was used in this study. Even though insulin-producing cells were destroyed morphologically and functionally, the effect of insulin was relatively dominant because of the concomitant severe impairments in glucagon and somatostatin by paracrined TNFα. This may provide an explanation for diabetes resistance in TNFα transgenic mice. The experiments of over-nutrition such as high-fat diet and high-sucrose one showed that these mice were also characterized by obesity resistance and fatty liver resistance. TNFα transgenic mice in the present study are considered of value for the model of fatty liver resistance against over-nutrition.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (3 results)

All 2016

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (1 results) (of which Invited: 1 results)

  • [Journal Article] Fulminant Type 1 Diabetes Mellitus with Anti-programmed Cell Death-1 Therapy2016

    • Author(s)
      Okamoto M, Okamoto M, Gotoh K, Masaki T, Ozeki Y, Ando H, Anai M, Sato A, Yoshida Y, Ueda S, Kakuma T, Shibata H
    • Journal Title

      J Diabetes Investig

      Volume: 7 Issue: 6 Pages: 915-918

    • DOI

      10.1111/jdi.12531

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pore alterations of the endothelial lining of rat fenestrated intestinal capillaries exposed to acute stress2016

    • Author(s)
      Aosa T, Chiba S, Kitamura H, Ina K, Tatsukawa S, Moriwaki C, Wei H, Gotoh K, Masaki T, Kakuma T, Shibata H, Fujikura Y
    • Journal Title

      Histol Histopathol

      Volume: 31 Pages: 807-817

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Presentation] 肥満「症」としての2型糖尿病ー最近の話題と課題ー2016

    • Author(s)
      加隈哲也
    • Organizer
      第54回日本糖尿病学会九州地方会
    • Place of Presentation
      鹿児島
    • Year and Date
      2016-10-14
    • Related Report
      2016 Annual Research Report
    • Invited

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Published: 2014-04-04   Modified: 2018-03-22  

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