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Induction of pancreatic beta cell expansion in transplanted mouse and human islets by targeting receptor of advanced glycation endo products

Research Project

Project/Area Number 25293281
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field General surgery
Research InstitutionFukuoka University

Principal Investigator

Yasunami Yohichi  福岡大学, 医学部, 教授 (00166521)

Co-Investigator(Kenkyū-buntansha) KODAMA Shohta  福岡大学, 医学部, 教授 (90549338)
ITOH Takeshi  福岡大学, 医学部, 講師 (70634400)
MISUMI Yoshio  福岡大学, 医学部, 准教授 (10148877)
Co-Investigator(Renkei-kenkyūsha) TANIGUCHI Masaru  国立研究開発法人理化学研究所, 統合生命医科学研究センター, グループディレクター (80110310)
WATARAI Hiroshi  東京大学, 医科学研究所, 准教授 (70415339)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2015: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2013: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Keywords膵島移植 / 糖尿病 / β細胞再生 / ヒト膵島 / 移植膵島再生 / 膵島再生
Outline of Final Research Achievements

The aim of the present study is to determine whether expansion of transplanted islets is induced when the injury of transplanted islets is prevented after transplantation. For those purposes, RAGE-/- vs wild-type mouse islets are used as donors since RAGE signals have been reported to be involved in beta cell failure. It was found that RAGE-/- islets are not only protected from the injuries but also expand after transplantation. The array analysis revealed that the beneficial effect of RAGE-/- islets was mediated through the upregulation of GLP-1 R expression. In addition, RAGE inhibitors including soluble form RAGE (sRAGE) was found to have the similar beneficial effect when applied to wild-type islets prior to transplantation. In case of human islets, the effect of sRAGE was not evident when treated human islets were grafted beneath the kidney capsule of STZ-diabetic NOD/scid mice and therefore, the effects of other RAGE inhibitors are currently under investigation.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (15 results)

All 2016 2015 2014 2013 Other

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 4 results,  Acknowledgement Compliant: 3 results) Presentation (9 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [Journal Article] Adjusting the 17β-Estradiol-to-Androgen Ratio Ameliorates Diabetic Nephropathy.2016

    • Author(s)
      Inada A, Inada O, Fujii NL, Nagafuchi S, Katsuta H, Yasunami Y, Matsubara T, Arai H, Fukatsu A, Nabeshima YI.
    • Journal Title

      J Am Soc Nephrol.

      Volume: 27

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Plasma biomarker for detection of early stage pancreatic cancer and risk factors for pancreatic malignancy using antibodies for apolipoprotein-AII isoforms.2015

    • Author(s)
      Honda K, Kobayashi M, Okusaka T, Rinaudo JA, Huang Y, Marsh T, Sanada M, Sasajima Y, Nakamori S, Shimahara M, Ueno T, Tsuchida A, Sata N, Ioka T, Yasunami Y, Kosuge T, Miura N, Kamita M, Sakamoto T, Shoji H, Jung G, Srivastava S, Yamada T.
    • Journal Title

      Scientific Reports

      Volume: Nov 9;5 Issue: 1 Pages: 15921-15921

    • DOI

      10.1038/srep15921

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] HMGB1-Mediated Early Loss of Transplanted Islets Is Prevented by Anti-IL-6R Antibody in Mice.2014

    • Author(s)
      Itoh T, Nitta T, Nishinakamura H, Kojima D, Mera T, Ono J, Kodama S, Yasunami Y.
    • Journal Title

      Pancreas.

      Volume: 44(1) Issue: 1 Pages: 166-71

    • DOI

      10.1097/mpa.0000000000000188

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Long-term outcomes of clinical transplantation of pancreatic islets with uncontrolled donors after cardiac death: a multicenter experience in Japan.2014

    • Author(s)
      Anazawa T, Saito T, Goto M, Kenmochi T, Uemoto S, Itoh T, Yasunami Y, Kenjo A, Kimura T, Ise K, Tsuchiya T, Gotoh M.
    • Journal Title

      Transplant Proc.

      Volume: 46(6) Issue: 6 Pages: 1980-4

    • DOI

      10.1016/j.transproceed.2014.06.006

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] HMGB1-mediated early loss of transplanted islets is prevented by anti-IL-6R antibody in mice.2014

    • Author(s)
      Itoh T, Nitta T, Nishinakamura H, Kojima D, Mera T, Ono J, Kodama S, Yasunami Y.
    • Journal Title

      Pancreas

      Volume: In press

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pretreatment of donor islets with the Na(+) /Ca(2+) exchanger inhibitor improves the efficiency of islet transplantation2013

    • Author(s)
      Mera T, Itoh T, Kita S, Kodama S, Kojima D, Nishinakamura H, Okamoto K, Ohkura M, Nakai J, Iyoda T, Iwamoto T, Matsuda T, Baba A, Omori K, Ono J, Watarai H, Taniguchi M, Yasunami Y.
    • Journal Title

      Am J Transplant

      Volume: 13 Issue: 8 Pages: 2154-2160

    • DOI

      10.1111/ajt.12306

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] ドナー膵島のRAGEを標的にした移植膵島障害の新規制御法2016

    • Author(s)
      安波洋一、棟居聖一、新田直柔、濱口百合子、山本靖彦
    • Organizer
      第43回日本膵・膵島移植研究会
    • Place of Presentation
      ホテルグランヴィア広島(広島市)
    • Year and Date
      2016-03-04
    • Related Report
      2015 Annual Research Report
  • [Presentation] Early loss of transplanted islets is prevented by targeting receptor for advanced glycation end products of donor islets in mice.2015

    • Author(s)
      Yasunami Y, Munesue S, Nitta N, Yamamoto Y.
    • Organizer
      IPITA - IXA - CTS 2015 Joint Congress
    • Place of Presentation
      Melbourne, Australia
    • Year and Date
      2015-11-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Rage of donor islets is a novel target to improve the efficiency of islet transplantation.2015

    • Author(s)
      Yasunami Y, Munesue S, Yamamoto Y, Yamamoto H.
    • Organizer
      12th International symposium on the Maillard Reaction
    • Place of Presentation
      東京大学 伊藤国際学術研究センター(東京)
    • Year and Date
      2015-09-01
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Addition of a specific Na+/Ca2+ exchanger inhibitor into collagenase solution prevents hypoxic damage of islets during isolation, facilitating to improve the efficiency of islet transplantation in mice.2014

    • Author(s)
      Itoh T, Mera T, Nishinakamura H, Kodama S, Yasunami Y.
    • Organizer
      The 2014 World Transplant Congress
    • Place of Presentation
      San Fransisco, USA
    • Year and Date
      2014-07-26 – 2014-07-31
    • Related Report
      2014 Annual Research Report
  • [Presentation] Expansion of Transplanted Islets by Co-transplantation of Adipose Tissue-derived Mesenchymal Stem Cells in Mice.2014

    • Author(s)
      Tanaka T, Itoh T, Matsumoto M, Kojima D, Mera T, Nishinakamura H, Kodama S, Ono J, Yanase T, Yasunami Y.
    • Organizer
      74th Scientific Sessions of American Diabetes Association
    • Place of Presentation
      San Fransisco, USA
    • Year and Date
      2014-06-13 – 2014-06-17
    • Related Report
      2014 Annual Research Report
  • [Presentation] 脂肪組織由来間葉系幹細胞による移植膵島生着率改善と膵島量増加効果2014

    • Author(s)
      田中 智子,伊東  威,松本 征仁,小島 大望,米良 利之,西中村 瞳,小玉 正太,小野 順子,柳瀬 敏彦,安波 洋一
    • Organizer
      第41回日本膵・膵島移植研究会
    • Place of Presentation
      名古屋
    • Related Report
      2013 Annual Research Report
  • [Presentation] Pretreatment of Donor Islets with a Specific Inhibitor of Na+/Ca2+ Exchanger Prior to Transplantation Improves the Efficiency of Islet Transplantation.2013

    • Author(s)
      Itoh T, Mera T, Kita S, Kojima D, Nishinakamura H, Ono J, Iwamoto T, Kodama S, Yasunami Y.
    • Organizer
      The 13th Congress of the Asian Society of Transplantation
    • Place of Presentation
      Kyoto, Japan
    • Related Report
      2013 Annual Research Report
  • [Presentation] The early loss of transplanted islets is prevented by targeting Na+/Ca2+ exchanger of donor islets prior to transplantation.2013

    • Author(s)
      Itoh T, Mera T, Kita S, Kodama S, Kojima D, Nishinakamura H, Iwamoto T, Omori K, Ono J, Watarai H, Taniguchi M, Yasunami Y.
    • Organizer
      The 14th World Congress of the International Pancreas and Islet Transplant Association (IPITA 2013)
    • Place of Presentation
      Monterey, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] A novel strategy to improve the efficiency of islet transplantation targeting Na+/Ca2+ exchanger of donor islets prior to transplantation.

    • Author(s)
      Yasunami Y.
    • Organizer
      The 12th Beta Cell Research and islet Transplantation Symposium
    • Place of Presentation
      Seoul, Korea
    • Related Report
      2013 Annual Research Report
    • Invited

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Published: 2013-05-21   Modified: 2019-07-29  

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