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Analysis of pathogenic mechanism by susceptibility genes of T2DM using human iPS cells.

Research Project

Project/Area Number 17K09882
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Endocrinology
Research InstitutionKobe University

Principal Investigator

Asahara] Shun-ichiro  神戸大学, 医学部附属病院, 助教 (00570342)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsヒトiPS細胞 / 糖尿病 / 膵β細胞 / 2型糖尿病感受性遺伝子 / 2型糖尿病 / iPS細胞
Outline of Final Research Achievements

It has been previously reported that KCNQ1 and EIF2AK4 were identified as T2DM susceptibility genes. We have clarified that the reduction of non-coding RNA Kcnq1ot1 expression induced pancratic beta cell failure in Kcnq1 mutant mice. Now, we analyzed the mechanism how T2DM susceptibility gene induces diabetes using human iPS cells derived pancreatic endocrine cell. As a result, we clarified that two iPS cells were differentiated into pancreatic endocrine cells. One cell has a risk allele of T2DM susceptibility gene, and the other without risl allele. The hiPS cell with a risk allele showed a reduced expression of Kcnq1ot1 compared to pancreatic endocrine cell without a risk allele.

Academic Significance and Societal Importance of the Research Achievements

今回の研究により、KCNQ1遺伝子において2型糖尿病発症のリスク因子となるSNPはKcnq1ot1発現低下に影響している可能性が考えられた。我々のこれまでの研究成果より、膵β細胞におけるp57発現増加が膵β細胞不全を介して2型糖尿病発症に繋がっていることがヒト細胞においても証明された。この結果、KCNQ1遺伝子のリスクアリルとなるSNPは2型糖尿病発症の予測因子として重要であり、将来的に検査項目の一つとなることが期待される。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (19 results)

All 2020 2019 2018 2017

All Journal Article (11 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 9 results,  Open Access: 9 results) Presentation (8 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] GCN2 regulates pancreatic β-cell mass by sensing intracellular amino acid levels.2020

    • Author(s)
      Kanno A, Asahara SI, Furubayashi A, Masuda K, Yoshitomi R, Suzuki E, Takai T, Kimura-Koyanagi M, Matsuda T, Bartolome A, Hirota Y, Yokoi N, Inaba Y, Inoue H, Matsumoto M, Inoue K, Abe T, Wei FY, Tomizawa K, Ogawa W, Seino S, Kasuga M, Kido Y.
    • Journal Title

      JCI Insight.

      Volume: 5 Issue: 9 Pages: 128820-128820

    • DOI

      10.1172/jci.insight.128820

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] En face slab optical coherence tomography imaging successfully monitors progressive degenerative changes in the innermost layer of the diabetic retina2020

    • Author(s)
      Katsuyama Atsuko、Kusuhara Sentaro、Asahara Shun-Ichiro、Nakai Shun-Ichiro、Mori Sotaro、Matsumiya Wataru、Miki Akiko、Kurimoto Takuji、Imai Hisanori、Kido Yoshiaki、Ogawa Wataru、Nakamura Makoto
    • Journal Title

      BMJ Open Diabetes Research & Care

      Volume: 8 Issue: 1 Pages: e001120-e001120

    • DOI

      10.1136/bmjdrc-2019-001120

    • NAID

      120006863549

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association between mean platelet volume in the pathogenesis of type 2 diabetes mellitus and diabetic macrovascular complications in Japanese patients.2019

    • Author(s)
      Inoue H, Saito M, Kouchi K, Asahara SI, Nakamura F, Kido Y.
    • Journal Title

      J. Diab. Invest.

      Volume: - Issue: 4 Pages: 938-945

    • DOI

      10.1111/jdi.13198

    • NAID

      120006876706

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Early administration of dapagliflozin preserves pancreatic β-cell mass through a legacy effect in a mouse model of type 2 diabetes2019

    • Author(s)
      Kanno A, Asahara SI, Kawamura M, Furubayashi A, Tsuchiya S, Suzuki E, Takai T, Koyanagi-Kimura M, Matsuda T, Okada Y, Ogawa W, Kido Y.
    • Journal Title

      J Diabetes Invest.

      Volume: 10 Issue: 3 Pages: 577-590

    • DOI

      10.1111/jdi.12945

    • NAID

      120006645694

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neuronatin and glucose-induced stress in pancreatic β-cells.2019

    • Author(s)
      Asahara SI
    • Journal Title

      J Diabetes Invest.

      Volume: 10 Issue: 3 Pages: 574-576

    • DOI

      10.1111/jdi.12993

    • NAID

      120006645695

    • Related Report
      2018 Research-status Report
    • Open Access
  • [Journal Article] PHD3 regulates glucose metabolism by suppressing stress-induced signalling and optimising gluconeogenesis and insulin signalling in hepatocytes.2018

    • Author(s)
      Yano H, Sakai M, Matsukawa T, Yagi T, Naganuma T, Mitsushima M, Iida S, Inaba Y, Inoue H, Unoki-Kubota H, Kaburagi Y, Asahara S, Kido Y, Minami S, Kasuga M, Matsumoto M.
    • Journal Title

      Sci Rep.

      Volume: 8 Issue: 1 Pages: 14290-14290

    • DOI

      10.1038/s41598-018-32575-z

    • NAID

      120006529679

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Docosahexaenoic Acid Reduces Palmitic Acid-Induced Endoplasmic Reticulum Stress in Pancreatic Β Cells.2018

    • Author(s)
      Suzuki E, Matsuda T, Kawamoto T, Takahashi H, Mieda Y, Matsuura Y, Takai T, Kanno A, Koyanagi-Kimura M, Asahara SI, Inoue H, Ogawa W, Kido Y.
    • Journal Title

      Kobe J Med Sci.

      Volume: 64

    • NAID

      120006523798

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] SGLT2 inhibitors and protection against pancreatic beta cell failure.2018

    • Author(s)
      Asahara SI, Ogawa W.
    • Journal Title

      Diabetol Int.

      Volume: 10 Issue: 1 Pages: 1-2

    • DOI

      10.1007/s13340-018-0374-y

    • Related Report
      2018 Research-status Report
  • [Journal Article] Casein kinase 2 phosphorylates and stabilizes C/EBPβ in pancreatic β cells.2018

    • Author(s)
      Takai T, Matsuda T, Matsuura Y, Inoue K, Suzuki E, Kanno A, Kimura-Koyanagi M, Asahara SI, Hatano N, Ogawa W, Kido Y.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 497 Issue: 1 Pages: 451-456

    • DOI

      10.1016/j.bbrc.2018.02.108

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] MTORC1 Regulates both General Autophagy and Mitophagy Induction after Oxidative Phosphorylation Uncoupling.2018

    • Author(s)
      2.Bartolomé A, García-Aguilar A, Asahara S, Kido Y, Guillén C, Pajvani UB, Benito M.
    • Journal Title

      Mol Cell Biol.

      Volume: 印刷中 Issue: 23

    • DOI

      10.1128/mcb.00441-17

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Histone deacetylase regulates insulin signaling via two pathways in pancreatic β cells.2017

    • Author(s)
      Kawada Y, Asahara SI, Sugiura Y, Sato A, Furubayashi A, Kawamura M, Bartolome A, Terashi-Suzuki E, Takai T, Kanno A, Koyanagi-Kimura M, Matsuda T, Hashimoto N, Kido Y.
    • Journal Title

      PLoS ONE

      Volume: 12 Issue: 9 Pages: e0184435-e0184435

    • DOI

      10.1371/journal.pone.0184435

    • NAID

      120006353753

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Effect of removal of glucotoxicity by SGLT2 inhibitor dapagliflozin on the gene expression in pancreatic beta cells2017

    • Author(s)
      Asahara S, Ohashi Y, Kido Y
    • Organizer
      IDF2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Analysis of Pathogenic Mechanism by Susceptibility Genes of T2DM Using Human iPS Cells2017

    • Author(s)
      Shimono N, Asahara S, Kido Y
    • Organizer
      77th Scientific Sessions of American Diabetes Association
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 膵β細胞の小胞体ストレス誘導性アポトーシスにおけるCK2βの役割2017

    • Author(s)
      高井智子、松田友和、井上佳歩、松浦有希、鈴木江美、神野歩、木村真希、淺原俊一郎、小川渉、木戸良明
    • Organizer
      第60回日本糖尿病学会年次学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 脂肪酸が膵β細胞の小胞体に及ぼす影響2017

    • Author(s)
      鈴木江美、松田友和、川本剛士、松浦有希、高井智子、神野歩、木村真希、淺原俊一郎、小川渉、木戸良明
    • Organizer
      第60回日本糖尿病学会年次学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] ヒトiPS細胞を用いた2型糖尿病発症機序の解明2017

    • Author(s)
      下野名奈子、淺原俊一郎、原瑞季、田中孝一、松田友和、木村真希、神野歩、高井智子、鈴木江美、青井貴之、木戸良明
    • Organizer
      第60回日本糖尿病学会年次学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 膵β細胞の小胞体ストレス誘導性アポトーシスにおけるCK2βの役割2017

    • Author(s)
      井上佳歩、高井智子、松田友和、鈴木江美、神野歩、木村真希、淺原俊一郎、木戸良明
    • Organizer
      第40回分子生物学会年会
    • Related Report
      2017 Research-status Report
  • [Presentation] 高脂肪食負荷GCN2欠損マウスの膵島におけるmTORC1シグナル調節機構の解明2017

    • Author(s)
      古林鮎子、神野歩、増田勝久、吉富理紗、木村真希、松田友和、淺原俊一郎、木戸良明
    • Organizer
      第40回分子生物学会年会
    • Related Report
      2017 Research-status Report
  • [Presentation] ヒトiPS細胞を用いた膵内分泌細胞への分化誘導法の確立2017

    • Author(s)
      山田瑞姫、淺原俊一郎、下野名奈子、田中孝一、松田友和、木村真希、神野歩、高井智子、鈴木江美、青井貴之、木戸良明
    • Organizer
      第40回分子生物学会年会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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