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Mechanism of differentiation of ductal cells to βcells.

Research Project

Project/Area Number 21790285
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field General medical chemistry
Research InstitutionKyushu University

Principal Investigator

INADA Akari  Kyushu University, 大学院・医学研究院, 准教授 (50448429)

Project Period (FY) 2009 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Keywords糖尿病 / β細胞 / 前駆細胞 / 膵管 / 分化
Research Abstract

We further studied the mechanism of differentiation of ductal cells to β cells. Although Pdx-1 is mainly restricted to β cells in the adult pancreas to regulate several β-cell specific genes, the increased Pdx-1 protein level in the duct has been reported in human obesity and the rodent regeneration mode. This coincident of increased Pdx-1 protein level imply that the regeneration mode the pancreas recapitulates embryonic development and that neogenesis contributes to the increased islet mass. To test our hypothesis that Pdx-1 expression in the duct could be critical factor for the differentiation of ductal cells to β cells, we generated duct-specific Pdx-1 knockout mice by crossing the CAII-Cre mice to Pdx-1flE2/flE2 mice, in which Pdx-1 expression in the duct was knocked out around the birth. Inactivation of Pdx-1 in the duct resulted in reduced β cells in normal growth which caused hyperglycemia and glucose tolerance. Moreover, in the regeneration study new β-cell formation was rarely seen in the adult. Thus, the activation of Pdx-1 in the duct is required for differentiation, and these differentiated β cells contribute to intensive β-cell growth in neonatal period and injury in the adult. Our study provides clear evidence of a compensatory function of a ductal-origin β cell.
These findings should encourage further exploration of pancreatic duct cells as a source for islet regeneration. Further attention on expansion and differentiation of these cells may facilitate β-cell replacement therapy for diabetes.

Report

(3 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report

Research Products

(49 results)

All 2011 2010 2009 Other

All Journal Article Presentation Book Remarks Patent(Industrial Property Rights)

  • [Journal Article] Different effects of islet transplantation and Detemir treatment on the reversal of streptozotocin induced diabetes associated with β cell regeneration.2010

    • Author(s)
      Inada A, Inada O, Fujii H, Akashi T, Sueishi K, Fukatsu A, Nagafuchi S
    • Journal Title

      Diabetol Int 1(1)

      Pages: 49-592

    • NAID

      10029620830

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Lack of evidence for recipient precursor cells replenishing beta cells in transplanted islets.2010

    • Author(s)
      Hamamoto Y, Akashi T, Inada A, Bonner-Weir S, Weir GC
    • Journal Title

      Cell Transplant 19(12)

      Pages: 1563-1572

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] 膵臓β細胞の新生と環境2010

    • Author(s)
      稲田明理
    • Journal Title

      日本女性科学者の会学術誌 11(1)

      Pages: 29-352

    • NAID

      130001077729

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Different effects of islet transplantation and Detemir treatment on the reversal of streptozotocin induced diabetes associated with β cell regeneration.2010

    • Author(s)
      Inada A, Inada O, Fujii H, Akashi T, Sueishi K, Fukatsu A, Nagafuchi S
    • Journal Title

      Diabetol Int

      Volume: 1-1 Pages: 49-59

    • NAID

      10029620830

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lack of evidence for recipient precursor cells replenishing beta cells in transplantedislets.2010

    • Author(s)
      Hamamoto Y, Akashi T, Inada A, Bonner-Weir S, Weir GC
    • Journal Title

      Cell Transplant

      Volume: 19-12 Pages: 1563-1572

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 膵臓β細胞の新生と環境2010

    • Author(s)
      稲田明理
    • Journal Title

      日本女性科学者の会学術誌

      Volume: 11-1 Pages: 29-35

    • NAID

      130001077729

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 膵臟β細胞の起源と新生2010

    • Author(s)
      稲田明理
    • Journal Title

      日本女性科学者の会学術誌 第10巻第1号 10

      Pages: 10-16

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 膵臓β細胞の起源と新生2009

    • Author(s)
      稲田明理
    • Journal Title

      日本女性科学者の会学術誌 10(1)

      Pages: 10-16

    • NAID

      130001238243

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Presentation] 膵管上皮細胞からβ細胞への新生について2011

    • Author(s)
      稲田明理
    • Organizer
      日本糖尿病学会(シンポジウム)
    • Place of Presentation
      札幌市教育文化会館(北海道)
    • Year and Date
      2011-05-21
    • Related Report
      2010 Annual Research Report
  • [Presentation] 膵管上皮細胞からβ細胞への分化メカニズム2011

    • Author(s)
      稲田明理
    • Organizer
      生活習慣病の分子細胞病態学研究会
    • Place of Presentation
      鎌倉プリンスホテル(神奈川県)
    • Year and Date
      2011-03-12
    • Related Report
      2010 Annual Research Report
  • [Presentation] 膵管上皮細胞からβ細胞への新生について2011

    • Author(s)
      稲田明理
    • Organizer
      日本糖尿病学会
    • Place of Presentation
      札幌(シンポジウム)
    • Related Report
      2010 Final Research Report
  • [Presentation] 膵管上皮細胞からβ細胞への分化メカニズム2011

    • Author(s)
      稲田明理
    • Organizer
      生活習慣病の分子細胞病態学研究会
    • Place of Presentation
      鎌倉
    • Related Report
      2010 Final Research Report
  • [Presentation] 膵管上皮細胞からβ細胞への分化メカニズム2010

    • Author(s)
      稲田明理
    • Organizer
      経済産業省 産学連携促進協議会
    • Place of Presentation
      バイオインダストリー協会(東京都)
    • Year and Date
      2010-12-10
    • Related Report
      2010 Annual Research Report
  • [Presentation] β細胞の新生と環境2010

    • Author(s)
      稲田明理
    • Organizer
      病態代謝研究会
    • Place of Presentation
      経団連会館(東京都)
    • Year and Date
      2010-10-16
    • Related Report
      2010 Annual Research Report
  • [Presentation] 膵管上皮細胞からβ細胞への分化メカニズム2010

    • Author(s)
      稲田明理
    • Organizer
      第13回Eastern Diabetes Conference
    • Place of Presentation
      福岡リーセントホテル(福岡県)
    • Year and Date
      2010-04-08
    • Related Report
      2010 Annual Research Report
  • [Presentation] Duct-specific deletion of Pdx1 after birth leads to transient hyperglycemia2010

    • Author(s)
      Guo L, Levine J, Inada A, Fujitani Y, Wright CV, Bonner-Weir S
    • Organizer
      American Diabetes Association 70th Scientific Sessions
    • Place of Presentation
      Orlando, USA
    • Related Report
      2010 Final Research Report
  • [Presentation] CAII positive pancreatic cells are progenitors for both endocrine and exocrine pancreas after birth2010

    • Author(s)
      Inada A
    • Organizer
      The 7th Catholic International Stem Cell Symposium
    • Place of Presentation
      Seoul, Korea(シンポジウム)
    • Related Report
      2010 Final Research Report
  • [Presentation] 細胞への分化メカニズム2010

    • Author(s)
      稲田明理
    • Organizer
      経済産業省産学連携促進協議会
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report
  • [Presentation] β細胞の新生と環境2010

    • Author(s)
      稲田明理
    • Organizer
      病態代謝研究会
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report
  • [Presentation] 膵管上皮細胞からβ細胞への分化メカニズム2010

    • Author(s)
      稲田明理
    • Organizer
      日本糖尿病学会
    • Place of Presentation
      岡山(シンポジウム)
    • Related Report
      2010 Final Research Report
  • [Presentation] 膵管上皮細胞からβ細胞への分化メカニズム2010

    • Author(s)
      稲田明理
    • Organizer
      第13回Eastern Diabetes Conference
    • Place of Presentation
      福岡
    • Related Report
      2010 Final Research Report
  • [Presentation] Duct-specific deletion of Pdxl after birth leads to transient hyperglycemia2010

    • Author(s)
      Guo L, Levine J, Inada A, Fujitani Y, Wright CV, Bonner-Weir S
    • Organizer
      American Diabetes Association 70th Scientific Sessions
    • Place of Presentation
      Orlando, USA
    • Related Report
      2010 Annual Research Report
  • [Presentation] 膵管上皮細胞からβ細胞への分化メカニズム2010

    • Author(s)
      稲田明理
    • Organizer
      日本糖尿病学会(シンポジウム)
    • Place of Presentation
      岡山コンベンションセンター(岡山県)
    • Related Report
      2010 Annual Research Report
  • [Presentation] 膵管上皮細胞に発現する転写因子Pdx-1の役割2009

    • Author(s)
      稲田明理
    • Organizer
      分子糖尿病学シンポジウム
    • Place of Presentation
      和歌山県立医科大学
    • Year and Date
      2009-12-12
    • Related Report
      2009 Annual Research Report
  • [Presentation] 膵β細胞の分化・再生機序の解明とその糖尿病治療への応用に関する研究2009

    • Author(s)
      稲田明理
    • Organizer
      北海道大学・九州大学合同活動報告会シンポジウム
    • Place of Presentation
      都市センターホテル,東京
    • Year and Date
      2009-12-10
    • Related Report
      2009 Annual Research Report
  • [Presentation] 膵管上皮細胞を起源とするβ細胞産生機構2009

    • Author(s)
      稲田明理
    • Organizer
      オープンユニバーシティ市民講座
    • Place of Presentation
      首都大学東京
    • Year and Date
      2009-11-25
    • Related Report
      2009 Annual Research Report
  • [Presentation] 膵管上皮細胞を起源とするβ細胞産生機構2009

    • Author(s)
      稲田明理
    • Organizer
      グローバルFUプログラムセミナー
    • Place of Presentation
      福岡大学
    • Year and Date
      2009-09-17
    • Related Report
      2009 Annual Research Report
  • [Presentation] 膵管上皮細胞を起源とするβ細胞産生機構2009

    • Author(s)
      稲田明理
    • Organizer
      糖尿病・血管代謝再生研究会
    • Place of Presentation
      金沢大学
    • Year and Date
      2009-07-17
    • Related Report
      2009 Annual Research Report
  • [Presentation] CAII positive pancreatic cells are progenitors for both endocrine and exocrine pancreasafter birth2009

    • Author(s)
      稲田明理
    • Organizer
      The 7^<th> Catholic International Stem Cell Symposium
    • Place of Presentation
      ソウル(韓国)
    • Year and Date
      2009-06-11
    • Related Report
      2009 Annual Research Report
  • [Presentation] 膵管上皮細胞に発現する転写因子Pdx-1の役割2009

    • Author(s)
      稲田明理、藤谷与士夫、川口義弥
    • Organizer
      分子糖尿病学
    • Place of Presentation
      和歌山(シンポジウム)
    • Related Report
      2010 Final Research Report
  • [Presentation] 膵β細胞の分化・再生機序の解明とその糖尿病治療への応用に関する研究2009

    • Author(s)
      稲田明理
    • Organizer
      北海道大学・九州大学合同活動報告会
    • Place of Presentation
      東京(シンポジウム)
    • Related Report
      2010 Final Research Report
  • [Presentation] 膵管上皮細胞を起源とするβ細胞産生機構2009

    • Author(s)
      稲田明理
    • Organizer
      糖尿病・血管代謝再生研究会
    • Place of Presentation
      金沢
    • Related Report
      2010 Final Research Report
  • [Book] 月刊糖尿病 1(4) iPS細胞と糖尿病治療への応用2009

    • Author(s)
      稲田明理
    • Publisher
      医学出版,東京
    • Related Report
      2010 Final Research Report
  • [Remarks] ホームページ等

    • Related Report
      2010 Final Research Report
  • [Remarks] 第10回日本再生医療学会総会YIA受賞講演 2011年3月授与式

    • URL

      http://www.aeplan.co.jp/jsrm2011/program/index.html#pr5

    • Related Report
      2010 Final Research Report
  • [Remarks] 平成18年度文部科学省・科学技術振興調整費「若手研究者の自立的研究環境整備促進」事業九州大学 次世代研究スーパースター養成プログラム

    • URL

      http://www.srp.kyushu-u.ac.jp/ssp_home/jtop.html

    • Related Report
      2010 Final Research Report
  • [Remarks] 日本女性科学者の会奨励賞受賞 2009年6月授与式、東京

    • URL

      http://www.sjws.jp/winning/index.html

    • Related Report
      2010 Final Research Report
  • [Remarks] 「血糖値を下げるβ細胞幹細胞出現を世界で初めて実証することに成功」2009年3月31日掲載、九州大学医学部ホームページ、トピックス

    • URL

      http://www.med.kyushu-u.ac.jp/m_annai/topics/annai_back.php?id=119

    • Related Report
      2010 Final Research Report
  • [Remarks] (1)第10回日本再生医療学会総会 YIA受賞講演

    • URL

      http://www.aeplan.co.jp/jsrm2011/program/index.html#pr5

    • Related Report
      2010 Annual Research Report
  • [Remarks] (2)平成18年度文部科学省・科学技術振興調整費「若手研究者の自立的研究環境整備促進」事業九州大学 次世代研究スーパースター養成プログラム

    • URL

      http://www.srp.kyushu-u.ac.jp/ssp_home/j_top.html

    • Related Report
      2010 Annual Research Report
  • [Remarks] (3)九州大学 研究者情報

    • URL

      http://hyoka.ofc.kyushu-u.ac.jp/search/details/K003231/index.html

    • Related Report
      2010 Annual Research Report
  • [Remarks] 日本女性科学者の会 奨励賞受賞 2009年6月授与式、東京

    • URL

      http://www.sjws.jp/winning/index.html

    • Related Report
      2009 Annual Research Report
  • [Remarks] 「血糖値を下げるβ細胞幹細胞出現を世界で初めて実証することに成功」2009年3月31日掲載、九州大学医学部ホームページ、トピムックス

    • URL

      http://www.med.kyushu-u.ac.jp/m_annai/topics/annai_back.php?id=119

    • Related Report
      2009 Annual Research Report
  • [Patent(Industrial Property Rights)] インスリン産生細胞誘導剤・糖尿病性腎症治療薬およびグルコースとりこみ促進剤2010

    • Inventor(s)
      稲田明理
    • Industrial Property Rights Holder
      稲田明理、九州大学
    • Filing Date
      2010-07-16
    • Related Report
      2010 Final Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 腎症関連遺伝子2010

    • Inventor(s)
      稲田明理
    • Industrial Property Rights Holder
      関西TLO
    • Acquisition Date
      2010-09-03
    • Related Report
      2010 Final Research Report
  • [Patent(Industrial Property Rights)] Nephropathy-Associated Gene2010

    • Inventor(s)
      稲田明理
    • Industrial Property Rights Holder
      関西TLO
    • Acquisition Date
      2010-06-29
    • Related Report
      2010 Final Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] インスリン産生細胞誘導剤・糖尿病性腎症治療薬およびグルコースとりこみ促進剤2010

    • Inventor(s)
      稲田明理
    • Industrial Property Rights Holder
      稲田明理
    • Filing Date
      2010-07-16
    • Related Report
      2010 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] インスリン産生細胞誘導剤・糖尿病性腎症治療薬およびグルコースとりこみ促進剤2009

    • Inventor(s)
      稲田明理
    • Industrial Property Rights Holder
      稲田明理、九州大学
    • Filing Date
      2009-07-16
    • Related Report
      2010 Final Research Report
  • [Patent(Industrial Property Rights)] インスリン産生細胞誘導剤・糖尿病性腎症治療薬およびグルコースとりこみ促進剤2009

    • Inventor(s)
      稲田明理
    • Industrial Property Rights Holder
      稲田明理
    • Filing Date
      2009
    • Related Report
      2009 Annual Research Report

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Published: 2009-03-31   Modified: 2018-02-26  

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