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Role of glucagon in diabetic cardiomyopathy and angiogenesis

Research Project

Project/Area Number 18H02805
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 53020:Cardiology-related
Research InstitutionNagoya University

Principal Investigator

MUROHARA TOYOAKI  名古屋大学, 医学系研究科, 教授 (90299503)

Co-Investigator(Kenkyū-buntansha) 大内 乗有  名古屋大学, 医学系研究科, 特任教授 (00595514)
坂東 泰子 (暮石泰子)  名古屋大学, 医学部附属病院, 講師 (60452190)
柴田 玲  名古屋大学, 医学系研究科, 特任教授 (70343689)
近藤 和久  名古屋大学, 医学系研究科, 講師 (90644659)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Keywords糖尿病 / 心不全 / インクレチン / GLP-1 / マイオカイン / アディポカイン / 血管新生 / 毛細血管 / グルカゴン / 心機能 / GLP-1受容体 / GLP-1受容体作動薬 / 心血管不全 / 血管内皮機能 / 血管再生 / 細胞内シグナル / 糖尿病性心筋症 / 毛細血管障害
Outline of Final Research Achievements

We studies the role of glucagon and GLP-1 in the regulation of myocardial angiogenesis and diabetic cardiomyopathy.
(1) Using glucagon and GLP-1 knockout mice, we demonstrated that physiological concentration of glucagon can protect against heart failure, while pharmacological high dose of glucagon is harmful to cardiac function (Nishimura et al. manuscript in revise)。
(2) Our group discovered a new myokine called myonectin that is released from the skeletal muscles during exercise. And we showed that myonectin is protective against myocardial ischemia/reperfusion-mediated heart failure. So myonectin can link the mechanism why regular exercise is healthy for cardiovascular disease.

Academic Significance and Societal Importance of the Research Achievements

近年高齢化を背景に心不全や2型糖尿病患者が増加している。糖尿病に心不全が合併すると予後が極めて悪くなることが知られている。糖尿病患者の中には、冠動脈病変が無くとも、心機能が低下している例があり「糖尿病性心筋症」と呼ばれているが、その機序は未だ不明な点が多い。我々は生理的な体内濃度のグルカゴンは心不全に対し保護的に働くこと, 高用量グルカゴンは心臓に対し障害的に働くことを初めて示した。現在インクレチン関連製剤が広く用いられており、我々の研究成果は臨床所見の理解に役立つ。また我々は、マイオカインの発見により、運動が心臓機能に良い影響を与えることの機序の一端を初めて解明することができた。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (26 results)

All 2021 2020 2019 2018

All Journal Article (14 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 14 results,  Open Access: 13 results) Presentation (12 results) (of which Int'l Joint Research: 9 results,  Invited: 1 results)

  • [Journal Article] Important Role of Concomitant Lymphangiogenesis for Reparative Angiogenesis in Hindlimb Ischemia.2021

    • Author(s)
      Pu Z, Shimizu Y, Tsuzuki K, Suzuki J, Hayashida R, Kondo K, Fujikawa Y, Unno K, Ohashi K, Takefuji M, Bando YK, Ouchi N, Calvert JW, Shibata R, Murohara T.
    • Journal Title

      Arterioscler Thromb Vasc Biol.

      Volume: - Issue: 6 Pages: 2006-2018

    • DOI

      10.1161/atvbaha.121.316191

    • NAID

      120007178394

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Therapeutic Angiogenesis Using Bone Marrow Mononuclear Cell Transplantation ― A New Standard Treatment for Thromboangiitis Obliterans? ―2020

    • Author(s)
      Shibata Rei、Yamaguchi Shukuro、Murohara Toyoaki
    • Journal Title

      Circulation Journal

      Volume: 84 Issue: 4 Pages: 549-550

    • DOI

      10.1253/circj.CJ-20-0137

    • NAID

      130007815657

    • ISSN
      1346-9843, 1347-4820
    • Year and Date
      2020-03-25
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Adipolin/C1q/Tnf-related protein 12 prevents adverse cardiac remodeling after myocardial infarction.2020

    • Author(s)
      Takikawa T, Ohashi K, Ogawa H, Otaka N, Kawanishi H, Fang L, Ozaki Y, Eguchi S, Tatsumi M, Takefuji M, Murohara T, Ouchi N.
    • Journal Title

      PLoS One.

      Volume: 15 Issue: 12 Pages: e0243483-e0243483

    • DOI

      10.1371/journal.pone.0243483

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Therapeutic angiogenesis using autologous adipose-derived regenerative cells in patients with critical limb ischaemia in Japan: a clinical pilot study2020

    • Author(s)
      Katagiri Takeshi、Kondo Kazuhisa、Shibata Rei、Hayashida Ryo、Shintani Satoshi、Yamaguchi Shukuro、Shimizu Yuuki、Unno Kazumasa、Kikuchi Ryosuke、Kodama Akio、Takanari Keisuke、Kamei Yuzuru、Komori Kimihiro、Murohara Toyoaki
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 16045-16045

    • DOI

      10.1038/s41598-020-73096-y

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] C1q/TNF-Related Protein 9 Promotes Revascularization in Response to Ischemia via an eNOS-Dependent Manner2020

    • Author(s)
      Yamaguchi Shukuro、Shibata Rei、Ohashi Koji、Enomoto Takashi、Ogawa Hayato、Otaka Naoya、Hiramatsu-Ito Mizuho、Masutomi Tomohiro、Kawanishi Hiroshi、Murohara Toyoaki、Ouchi Noriyuki
    • Journal Title

      Frontiers in Pharmacology

      Volume: 11 Pages: 1313-1313

    • DOI

      10.3389/fphar.2020.01313

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Therapeutic Angiogenesis with Somatic Stem Cell Transplantation2020

    • Author(s)
      Murohara Toyoaki
    • Journal Title

      Korean Circulation Journal

      Volume: 50 Issue: 1 Pages: 12-12

    • DOI

      10.4070/kcj.2019.0288

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Adipolin/CTRP12 protects against pathological vascular remodeling through suppression of smooth muscle cell growth and macrophage inflammatory response.2019

    • Author(s)
      Ogawa H, Ohashi K, Ito M, Shibata R, Kanemura N, Yuasa D, Kambara T, Matsuo K, Hayakawa S, Hiramatsu-Ito M, Otaka N, Kawanishi H, Yamaguchi S, Enomoto T, Abe T, Kaneko M, Takefuji M, Murohara T, Ouchi N.
    • Journal Title

      Cardiovasc Res.

      Volume: in press Issue: 1 Pages: 237-249

    • DOI

      10.1093/cvr/cvz074

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Protein Kinase N Promotes Stress-Induced Cardiac Dysfunction Through Phosphorylation of Myocardin-Related Transcription Factor A and Disruption of Its Interaction With Actin.2019

    • Author(s)
      Sakaguchi T, Takefuji M, Wettschureck N, Hamaguchi T, Amano M, Kato K, Tsuda T, Eguchi S, Ishihama S, Mori Y, Yura Y, Yoshida T, Unno K, Okumura T, Ishii H, Shimizu Y, Bando YK, Ohashi K, Ouchi N, Enomoto A, Offermanns S, Kaibuchi K, Murohara T.
    • Journal Title

      Circulation.

      Volume: 140 Issue: 21 Pages: 1737-1752

    • DOI

      10.1161/circulationaha.119.041019

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Roles of the Mesenchymal Stromal/Stem Cell Marker Meflin in Cardiac Tissue Repair and the Development of Diastolic Dysfunction.2019

    • Author(s)
      Hara A, Kobayashi H, Asai N, Saito S, Higuchi T, Kato K, Okumura T, Bando YK, Takefuji M, Mizutani Y, Miyai Y, Saito S, Maruyama S, Maeda K, Ouchi N, Nagasaka A, Miyata T, Mii S, Kioka N, Worthley DL, Murohara T, Takahashi M, Enomoto A.
    • Journal Title

      Circ. Res.

      Volume: 125 Issue: 4 Pages: 414-430

    • DOI

      10.1161/circresaha.119.314806

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cardiomyocytes capture stem cell-derived, anti-apoptotic microRNA-214 via clathrin-mediated endocytosis in acute myocardial infarction.2019

    • Author(s)
      Eguchi S, Takefuji M, Sakaguchi T, Ishihama S, Mori Y, Tsuda T, Takikawa T, Yoshida T, Ohashi K, Shimizu Y, Hayashida R, Kondo K, Bando YK, Ouchi N, Murohara T.
    • Journal Title

      J Biol Chem.

      Volume: 294 Issue: 31 Pages: 11665-11674

    • DOI

      10.1074/jbc.ra119.007537

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anti-angiogenic isoform of vascular endothelial growth factor-A in cardiovascular and renal disease.2019

    • Author(s)
      Kikuchi R, Stevens M, Harada K, Oltean S, Murohara T.
    • Journal Title

      Adv. Clin. Chem.

      Volume: 88 Pages: 1-33

    • DOI

      10.1016/bs.acc.2018.10.001

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Association between the ratio of anti-angiogenic isoform of VEGF-A to total VEGF-A and adverse clinical outcomes in patients after acute myocardial infarction.2018

    • Author(s)
      Harada K, Kikuchi R, Ishii H, Shibata Y, Suzuki S, Tanaka A, Suzuki A, Hirayama K, Murohara T.
    • Journal Title

      Int. J. Cardiol. Heart Vasc.

      Volume: 19 Pages: 3-7

    • DOI

      10.1016/j.ijcha.2018.03.004

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impact of Lymphangiogenesis on Cardiac Remodeling After Ischemia and Reperfusion Injury.2018

    • Author(s)
      Shimizu Y, Polavarapu R, Eskla KL, Pantner Y, Nicholson CK, Ishii M, Brunnhoelzl D, Mauria R, Husain A, Naqvi N, Murohara T, Calvert JW.
    • Journal Title

      J Am Heart Assoc.

      Volume: 7 Issue: 19

    • DOI

      10.1161/jaha.118.009565

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Myonectin Is an Exercise-Induced Myokine That Protects the Heart From Ischemia-Reperfusion Injury.2018

    • Author(s)
      Otaka N, Shibata R, Ohashi K, Uemura Y, Kambara T, Enomoto T, Ogawa H, Ito M, Kawanishi H, Maruyama S, Joki Y, Fujikawa Y, Narita S, Unno K, Kawamoto Y, Murate T, Murohara T, Ouchi N.
    • Journal Title

      Circ Res.

      Volume: 123 Issue: 12 Pages: 1326-1338

    • DOI

      10.1161/circresaha.118.313777

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] Clathrin-mediated Endocytosis Plays a Key Role in Stem Cell Therapy for Ischemic Heart Disease2020

    • Author(s)
      Shunsuke Eguchi, Mikito Takefuji, Toyoaki Murohara
    • Organizer
      American Heart Association (AHA)
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Impact of Circadian Rhythm Disorders on Reparative Angiogenesis2020

    • Author(s)
      Kazuhito Tsuzuki, Yuuki Shimizu, Zhongyue Pu, Junya Suzuki, Shukuro Yamaguchi, Rei Shibata, Toyoaki Murohara
    • Organizer
      American Heart Association (AHA)
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Safety Evaluation of Therapeutic Angiogenesis With Adipose-derived Regenerative Cells for Ischemic Limb in a Tumor Bearing Model2020

    • Author(s)
      Junya Suzuki, Yuuki Shimizu, Kazuhito Tsuzuki, Zhongyue Pu, Shukuro Yamaguchi, Rei Shibata, Toyoaki Murohara
    • Organizer
      American Heart Association (AHA)
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Glucose-dependent insulinotropic peptide is essential for maintenance of cardiac lipid metabolism via FGF21-dependent pathway2019

    • Author(s)
      Y Remina, Y Kureishi Bando, R Ozaki, T Kamihara, K Nishimura, T Murohara
    • Organizer
      欧州心臓病学会
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] C1q/Tumor Necrosis Factor-Related Protein 9 Stimulates Revascularization in Response to Ischemia Through an Endothelial Nitric Oxide Synthase-Dependent Pathway2019

    • Author(s)
      Shukuro Yamaguchi ,Rei Shibata ,Koji Ohashi ,Toyoaki Murohara, Noriyuki Ouchi
    • Organizer
      アメリカ心臓協会年次集会
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Implantation of Adipose-Derived Regenerative Cells Promotes Coordinated Angiogenesis and Lymphangiogenesis in Reparative Hind Limb Ischemia Model2019

    • Author(s)
      Zhongyue Pu ,Yuuki Shimizu ,Kazuhito Tsuzuki ,Junya Suzuki, Toyoaki Murohara
    • Organizer
      アメリカ心臓協会年次集会
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Impaired Autophagic Off-rate is Responsible for Cardiac Aging via Oxidative Stress2019

    • Author(s)
      Yasuko K Bando ,Takahiro Kamihara ,Kazuyuki Nishimura ,Yasheng Retina, Toyoaki Murohara
    • Organizer
      アメリカ心臓協会年次集会
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Glucagon acts as a guardian of the heart against catecholamine elevation.2019

    • Author(s)
      西村和之、板東泰子、室原豊明 他
    • Organizer
      第83回日本循環器学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Glucose metabolism in failing hearts.2019

    • Author(s)
      Toyoaki Murohara
    • Organizer
      International Society of Heart Research, Beijing World Congress XXIII
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Lymphangiogenesis contributes to the ischemia induced angiogenesis in HLI via clearance of inflammation.2019

    • Author(s)
      Zhongyue Pu, Yuuki Shimizu, Toyoaki Murohara
    • Organizer
      第83回日本循環器学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] C1q/TNF-related protein 9 enhances ischemia-induced revascularization through an eNOS-dependent pathway2019

    • Author(s)
      山口淑郎,柴田玲,大橋浩二,室原豊明,大内乗有
    • Organizer
      第83回日本循環器学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Glucagon acts as a guardian of the heart against catecholamine surge.2018

    • Author(s)
      Kazuyuki Nishimura, Yasuko Bando, Takatoshi Kamihara, Remina Yasheng, Toyoaki Murohara
    • Organizer
      European Society of Cardiology, Congress 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2022-01-27  

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