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ChREBP regulates blood glucose level via the expression of GLUT2

Research Project

Project/Area Number 16K01820
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Applied health science
Research InstitutionHealth Sciences University of Hokkaido (2018)
Kobe University (2016-2017)

Principal Investigator

Nakagawa Tsutomu  北海道医療大学, 薬学部, 准教授 (50722063)

Research Collaborator UYEDA kosaku  
SAKIYAMA haruhiko  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsChREBP / GLUT2 / 糖尿病
Outline of Final Research Achievements

ChREBP KO mice showed a decrease in GLUT2 mRNA expression levels in all tissues, except the kidney, compared to the wild type mice. Next, to investigate whether ChREBP binds to the active promoter region of GLUT2, a series of reporter plasmids were constructed, each with a 500 bp insert, located 2.0 kb upstream and up to 500 bp downstream of the transcription start site of GLUT2 gene. The promoter activities of ChREBP were measured in HepG2 cells and not all reporter vectors used in this study demonstrated active promoter-binding interactions. Furthermore, experiments using ChREBP-overexpressed stable cell line, under low glucose condition, showed no correlation between mRNA level of GLUT2 and protein level of ChREBP. These results suggest that ChREBP did not regulate GLUT2 expression directly, but that glucose metabolite(s), which were increased in cells by ChREBP activation, might be involved in the regulation of GLUT2 expression.

Academic Significance and Societal Importance of the Research Achievements

GLUT2の発現量がChREBP KOマウスの様々な臓器において減少したことから、ChREBPがGLUT2の発現を制御していることが明らかとなった。この結果は、ChREBPを標的とした血糖降下薬の開発につながると考えられるため、糖尿病治療に新たな選択肢を加えることができるという点において社会的意義は大きいと考えられる。また、本研究によりChREBPは血糖調節機能を有することが明らかとなり、これまでに明らかになっている生理機能であるグルコース代謝と脂質合成の他に、血糖調節機能というChREBPの新たな生理機能を明らかにしたという点において学術的意義も高いと考えられる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (19 results)

All 2018 2017 2016 Other

All Int'l Joint Research (1 results) Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Acknowledgement Compliant: 1 results) Presentation (7 results) (of which Int'l Joint Research: 1 results) Remarks (3 results)

  • [Int'l Joint Research] UT Southwestern Medical Center(米国)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Association of Expression Levels or Activation Status of STAT3 with Treatment Outcomes of Sunitinib in Patients with Renal Cell Carcinoma.2018

    • Author(s)
      Yamamoto K., Hara T., Nakagawa T., Hirai M., Miyake H., Fujisawa M., Yano I.
    • Journal Title

      Targeted Oncology

      Volume: 13 Issue: 3 Pages: 371-378

    • DOI

      10.1007/s11523-018-0563-4

    • NAID

      120006649622

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prostaglandin E1 reduces the keratinocyte toxicity of sorafenib by maintaining signal transducer and activator of transcription 3 (STAT3) activity and enhancing the cAMP response element binding protein (CREB) activity.2017

    • Author(s)
      Shichiri H., Yamamoto K., Tokura M., Ishida T., Uda A., Bito T., Nishigori C., Nakagawa T., Hirano T., Yano I., Hirai M.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 485 Issue: 2 Pages: 227-233

    • DOI

      10.1016/j.bbrc.2017.02.107

    • NAID

      120006733140

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Association of Single Nucleotide Polymorphisms in <i>STAT3</i>, <i>ABCB1</i>, and <i>ABCG2</i> with Stomatitis in Patients with Metastatic Renal Cell Carcinoma Treated with Sunitinib: A Retrospective Analysis in Japanese Patients2017

    • Author(s)
      Watanabe A., Yamamoto K., Ioroi T., Hirata S., Harada K., Miyake H., Fujisawa M., Nakagawa T., Yano I., Hirai M.
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 40 Issue: 4 Pages: 458-464

    • DOI

      10.1248/bpb.b16-00875

    • NAID

      130005530145

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Compatibility and Stability of Nab-Paclitaxel in Combination with Other Drugs.2017

    • Author(s)
      Mizuta N., Nakagawa T., Yamamoto K., Nishioka T., Kume M., Makimoto H., YANO I., Minami H., Hirai M.
    • Journal Title

      Kobe Journal of Medical Sciences

      Volume: 63 Pages: 9-16

    • NAID

      120006329054

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effects of Ascorbyl-2-phosphate Magnesium on Human Keratinocyte Toxicity and Pathological Changes by Sorafenib2017

    • Author(s)
      Yamamoto K., Shichiri H., Ishida T., Kaku K., Nishioka T., Kume M., Makimoto H., Nakagawa T., Hirano T., Bito T., Nishigori C., Yano I., Hirai M.
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 40 Issue: 9 Pages: 1530-1536

    • DOI

      10.1248/bpb.b17-00386

    • NAID

      130006038784

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] シグナル伝達因子に起因する間質性肺炎発症メカニズム2017

    • Author(s)
      山本和宏,中川勉,矢野育子,平井みどり
    • Journal Title

      BIO Clinica

      Volume: 6 Pages: 121-125

    • Related Report
      2016 Research-status Report
  • [Journal Article] 転写因子ChREBPを標的とした生活習慣病の予防法及び治療薬の開発2017

    • Author(s)
      崎山晴彦,中川勉,江口裕伸,吉原大作,藤原範子,鈴木敬一郎
    • Journal Title

      細胞

      Volume: 49 Pages: 81-84

    • Related Report
      2016 Research-status Report
    • Acknowledgement Compliant
  • [Journal Article] Metabolite Regulation of Nuclear Localization of Carbohydrate-response Element-binding Protein (ChREBP): ROLE OF AMP AS AN ALLOSTERIC INHIBITOR2016

    • Author(s)
      Sato S, Jung H, Nakagawa T, Pawlosky R, Takeshima T, Lee WR, Sakiyama H, Laxman S, Wynn RM, Tu BP, MacMillan JB, De Brabander JK, Veech RL, Uyeda K
    • Journal Title

      Journal of Biological Chemistry

      Volume: 291 Issue: 20 Pages: 10515-10527

    • DOI

      10.1074/jbc.m115.708982

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] ChREBP欠損マウスが有する抗肥満作用の検討2018

    • Author(s)
      崎山 晴彦, 中川 勉, 井上 美奈子, 江口 裕伸, 吉原 大作, 藤原 範子, 鈴木 敬一郎
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Carbohydrate response element-binding protein (ChREBP)の活性制御に及ぼすO-GlcNAc修飾の影響2017

    • Author(s)
      中川勉,崎山晴彦,山本和宏,藤原範子,鈴木敬一郎,平井みどり
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2017-09-25
    • Related Report
      2016 Research-status Report
  • [Presentation] Association of Single Nucleotide Polymorphisms in STAT3, ABCB1, and ABCG2 with Stomatitis in Patients with Metastatic Renal Cell Carcinoma Treated with Sunitinib: A Retrospective Analysis in Japanese Patients2017

    • Author(s)
      Watanabe A, Yamamoto K, Ioroi T, Hirata S, Harada K, Miyake H, Fujisawa M, Nakagawa T, Yano I, Hirai M
    • Organizer
      The 5th International Symposium of Training Plan for Oncology Professionals
    • Place of Presentation
      シェラトン都ホテル大阪(大阪府大阪市)
    • Year and Date
      2017-03-11
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] ChREBPのグルコース濃度依存的なDNA結合はO-GlcNAc修飾により制御される2017

    • Author(s)
      中川勉、吉村友希、崎山晴彦、中川孝俊、山本和宏、矢野育子、藤原範子、朝日通雄、鈴木敬一郎、平井みどり
    • Organizer
      第64回日本生化学会近畿支部例会
    • Related Report
      2017 Research-status Report
  • [Presentation] 転写因子ChREBP欠損マウスにおける抗肥満効果2017

    • Author(s)
      崎山晴彦、井上美奈子、中川勉、江口裕伸、吉原大作、藤原範子、鈴木敬一郎
    • Organizer
      ConBio2017
    • Related Report
      2017 Research-status Report
  • [Presentation] エイコサペンタエン酸(EPA)が血清中性脂肪を低下させる分子メカニズムの解明2017

    • Author(s)
      中川勉,崎山晴彦,山本和宏,藤原範子,鈴木敬一郎,平井みどり
    • Organizer
      第63回日本生化学会近畿支部例会
    • Place of Presentation
      神戸薬科大学(兵庫県神戸市)
    • Related Report
      2016 Research-status Report
  • [Presentation] 不飽和脂肪酸が血清中性脂肪を低下させる分子メカニズムの解明:ChREBPの抑制機構の解明2017

    • Author(s)
      中川勉
    • Organizer
      第16回 油脂優秀論文賞受賞講演会
    • Place of Presentation
      奈良女子大学(奈良県奈良市)
    • Related Report
      2016 Research-status Report
  • [Remarks] 北海道医療大学 薬剤学(製剤学)研究内容

    • URL

      http://www.hoku-iryo-u.ac.jp/~siba/research.html

    • Related Report
      2018 Annual Research Report
  • [Remarks] 神戸大学大学院医学研究科 薬物動態学・薬剤学分野

    • URL

      http://www.med.kobe-u.ac.jp/yakudo/

    • Related Report
      2017 Research-status Report
  • [Remarks] 神戸大学病院薬剤部ホームページ

    • URL

      http://www.hosp.kobe-u.ac.jp/yakuzai/Pharm/index1.htm

    • Related Report
      2016 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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