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Glucose metabolism in ghrelin conditional KO mice

Research Project

Project/Area Number 23591320
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Metabolomics
Research InstitutionJichi Medical University

Principal Investigator

DEZAKI Katsuya  自治医科大学, 医学部, 准教授 (90337329)

Co-Investigator(Kenkyū-buntansha) YADA Toshihiko  自治医科大学, 医学部, 教授 (60166527)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords糖代謝 / インスリン分泌 / グレリン
Research Abstract

Ghrelin reportedly restricts insulin release in islet b-cells via Gi-proteins and thereby regulates glucose homeostasis. This study explored whether ghrelin regulates cAMP signaling and whether this regulation induces insulinostatic cascade in islet b-cells. Furthermore, this study aimed to clarify whether ghrelin counteracts effects of GLP-1, a physiological incretin hormone that promote glucose-induced insulin release in rat islet b-cells.
Ghrelin directly interacts with b-cells to attenuate glucose-induced cAMP production and PKA activation, which lead to activation of Kv channels and suppression of glucose-induced [Ca2+]i increase and insulin release. Ghrelin potently attenuates GLP-1-induced cAMP production, [Ca2+]i increases and insulin release in b-cells. These findings indicate that interaction between ghrelin and GLP-1 plays an important role in physiological regulation of glucose-induced insulin release.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (41 results)

All 2014 2013 2012 2011

All Journal Article (17 results) (of which Peer Reviewed: 17 results,  Open Access: 1 results) Presentation (20 results) Book (4 results)

  • [Journal Article] Involvement of cAMP-EPAC-TRPM2 activation in glucose- and incretin-induced insulin secretion2014

    • Author(s)
      Yoshida M, Dezaki K, Uchida K, Kodera S, Lam NV, Ito K, Rita RS, Yamada H, Shimomura K, Ishikawa SE, Sugawara H, Kawakami M, Tominaga M, Yada T, Kakei M
    • Journal Title

      Diabetes

      Volume: (Epub ahead of print) Issue: 10 Pages: 3394-3403

    • DOI

      10.2337/db13-1868

    • NAID

      40020531124

    • Related Report
      2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Involvement of cAMP-EPAC-TRPM2 activation in glucose- and incretin-induced insulin secretion.2014

    • Author(s)
      Masashi Yoshida
    • Journal Title

      Diabetes

      Volume: 63

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chronic exposure to valproic acid promotes insulin release, reduces KATP channel current and does not affect Ca2+ signaling in mouse islets.2014

    • Author(s)
      Kazunori Manaka
    • Journal Title

      J Phys Sci

      Volume: 64 Issue: 1 Pages: 77-83

    • DOI

      10.1007/s12576-013-0294-3

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Serum ghrelin levels partially recover with the recovery of appetite and food intake after total gastrectomy.2014

    • Author(s)
      Masaru Koizumi
    • Journal Title

      Surg Today

      Volume: 44 Issue: 11 Pages: 2131-2137

    • DOI

      10.1007/s00595-014-0873-9

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A new experimental model of ATP-sensitive K<sup>+</sup> channel-independent insulinotropic action of glucose: a permissive role of cAMP for triggering of insulin release from rat pancreatic &beta;-cells2013

    • Author(s)
      Masahiro Takei
    • Journal Title

      Endocrine Journal

      Volume: 60 Issue: 5 Pages: 599-607

    • DOI

      10.1507/endocrj.EJ12-0388

    • NAID

      10031184527

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] The ghrelin function in insulin release and glucose metabolism.2013

    • Author(s)
      Katsuya Dezaki
    • Journal Title

      Endocr Dev

      Volume: 25 Pages: 135-143

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Insulin activates vagal afferent neurons including those innervating pancreas via insulin cascade and Ca2+ influx: its dysfunction in IRS2-KO mice with hyperphagic obesity.2013

    • Author(s)
      Yusaku Iwasaki
    • Journal Title

      PLoS One

      Volume: 8 Issue: 6 Pages: e67198-e67198

    • DOI

      10.1371/journal.pone.0067198

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ghrelin counteracts salt-induced hypertension via promoting diuresis and renal nitric oxide production in Dahl rats2013

    • Author(s)
      Aoki H, Nakata M, Dezaki K, Lu M, Gantulga D, Yamamoto K, Shimada K, Kario K, Yada T
    • Journal Title

      Endocrine Journal

      Volume: 60 Issue: 5 Pages: 571-581

    • DOI

      10.1507/endocrj.EJ12-0371

    • NAID

      10031184524

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bupropion can close KATP channel and induce insulin secretion2013

    • Author(s)
      Yang Y, Shimomura K, Sakuma K, Maejima Y, Iwasaki Y, Galvanovskis J, Dezaki K, Nakata M, Yada T
    • Journal Title

      J Pediatr Endocrinol Metab

      Volume: 26(3-4) Issue: 3-4 Pages: 343-346

    • DOI

      10.1515/jpem-2012-0295

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Inhibition of insulin secretion from rat pancreatic islets by dexmedetomidine and medetomidine, two sedatives frequently used in clinical settings2013

    • Author(s)
      Shiho Yamato-Kodera
    • Journal Title

      Endocrine Journal

      Volume: 60 Issue: 3 Pages: 337-346

    • DOI

      10.1507/endocrj.EJ12-0308

    • NAID

      10031170619

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Islet β-cell ghrelin signaling for inhibition of insulin secretion.2012

    • Author(s)
      Katsuya Dezaki
    • Journal Title

      Methods Enzymol

      Volume: 514 Pages: 317-331

    • DOI

      10.1016/b978-0-12-381272-8.00020-9

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Exogenous and endogenous ghrelin counteracts GLP-1 action to stimulate cAMP signaling and insulin secretion in islet β-cells2012

    • Author(s)
      Damdindorj B, Dezaki K, Kurashina T, Sone H, Rita R, Kakei M, Yada T
    • Journal Title

      FEBS Lett

      Volume: 586(16) Issue: 16 Pages: 2555-2562

    • DOI

      10.1016/j.febslet.2012.06.034

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Early-phase occurrence of K+ and Cl- efflux in addition to Ca2+ mobilization is a prerequisite to apoptosis in HeLa cells.2012

    • Author(s)
      出崎克也、前野恵美、佐藤かお理、秋田天平、岡田泰伸
    • Journal Title

      Apoptosis

      Volume: 17 Issue: 8 Pages: 821-831

    • DOI

      10.1007/s10495-012-0716-3

    • Related Report
      2012 Research-status Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Ghrelin attenuates cAMP-PKA signaling to evoke insulinostatic cascade in isletβ-cells2011

    • Author(s)
      Dezaki K, Damdindorj B, Sone H, Dyachok O, Tengholm A, Gylfe E, Kurashina T, Yoshida M, Kakei M, Yada T
    • Journal Title

      Diabetes

      Volume: 60 Issue: 9 Pages: 2315-2324

    • DOI

      10.2337/db11-0368

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Ghrelin attenuates cAMP-PKA signaling to evoke insulinostatic cascade in islet β-cells.2011

    • Author(s)
      Katsuya Dezaki
    • Journal Title

      Diabetes

      Volume: 60 Pages: 2315-2324

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Postoperative weight loss does not resolve after esophagectomy despite normal serum ghrelin levels.2011

    • Author(s)
      Masaru Koizumi
    • Journal Title

      Ann Thorac Surg

      Volume: 91 Pages: 1032-1037

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Lack of TRPM2 impaired insulin secretion and glucose metabolisms in mice.2011

    • Author(s)
      Kunitoshi Uchida
    • Journal Title

      Diabetes

      Volume: 60 Pages: 119-126

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] グレリンはGLP-1のインクレチン効果を抑制する2014

    • Author(s)
      出崎克也
    • Organizer
      第91回日本生理学会大会
    • Place of Presentation
      鹿児島
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] Zucker fattyラットの肥満初期における血中グレリン動態2013

    • Author(s)
      出崎克也
    • Organizer
      第34回日本肥満学会
    • Place of Presentation
      東京
    • Related Report
      2013 Final Research Report
  • [Presentation] GLP-1によるインスリン分泌に対するグレリンの抑制作用2013

    • Author(s)
      出崎克也
    • Organizer
      第56回日本糖尿病学会年次学術集会
    • Place of Presentation
      熊本
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] グレリン受容体シグナルとしての膵β細胞Kvチャネル2013

    • Author(s)
      出崎克也
    • Organizer
      第90回日本生理学会大会
    • Place of Presentation
      東京
    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Presentation] 膵β細胞における新規GLP-1メカニズムとしてのTrpm2チャネル2013

    • Author(s)
      吉田 昌史
    • Organizer
      第56回日本糖尿病学会年次学術集会
    • Place of Presentation
      熊本
    • Related Report
      2013 Annual Research Report
  • [Presentation] 抗鬱剤ブプロピオンは膵β細胞KATPチャネルに直接作用してインスリン分泌を惹起する2013

    • Author(s)
      楊 怡飛
    • Organizer
      第56回日本糖尿病学会年次学術集会
    • Place of Presentation
      熊本
    • Related Report
      2013 Annual Research Report
  • [Presentation] Zucker fatty ラットの肥満初期における血中グレリン動態2013

    • Author(s)
      出崎 克也
    • Organizer
      第34回日本肥満学会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] 胃全摘ラットの摂食・体重低下に対する六君子湯の改善効果2013

    • Author(s)
      田口 昌延
    • Organizer
      第34回日本肥満学会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] Glucose-induced insulin release is enhanced by blockade of Kv2.1 channels in β-cells2013

    • Author(s)
      Rauza Sukma Rita
    • Organizer
      第34回日本肥満学会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] Kv2.1チャネル阻害による膵島インスリン分泌亢進2013

    • Author(s)
      Rauza Sukma Rita
    • Organizer
      第90回日本生理学会大会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] グレリンによる膵β細胞cAMPシグナルを介したインスリン分泌抑制2013

    • Author(s)
      出崎 克也
    • Organizer
      第86回日本薬理学会年会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] グレリンによるβ細胞cAMPシグナルを介したグルコース誘発インスリン分泌抑制2012

    • Author(s)
      出崎克也
    • Organizer
      第55回日本糖尿病学会年次学術集会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Presentation] Ghrelin attenuates glucose-dependent ability of GLP-1 to increase cAMP, cytosolic Ca2+ and insulin release in islet β-cells.2012

    • Author(s)
      Boldbaatar Damdindorj
    • Organizer
      The 48th EASD Annual Meeting
    • Place of Presentation
      Berlin
    • Related Report
      2012 Research-status Report
  • [Presentation] Activation of nonselective cation channels via cAMP-Epac2 pathway is involved in exendin-4 potentiated insulin secretion.2012

    • Author(s)
      Masashi Yoshida
    • Organizer
      The 48th EASD Annual Meeting
    • Place of Presentation
      Berlin
    • Related Report
      2012 Research-status Report
  • [Presentation] グレリンの膵β細胞インスリン分泌抑制作用におけるcAMPシグナルの関与2012

    • Author(s)
      出崎 克也
    • Organizer
      第33回日本肥満学会
    • Place of Presentation
      京都
    • Related Report
      2012 Research-status Report
  • [Presentation] 2型糖尿病ラット膵β細胞における電位依存性Kv2.1チャネルの発現・機能亢進2011

    • Author(s)
      出崎 克也
    • Organizer
      第54回日本糖尿病学会年次学術集会
    • Place of Presentation
      札幌
    • Related Report
      2011 Research-status Report
  • [Presentation] 膵β細胞イオンチャネルに対するグレリンの効果2011

    • Author(s)
      出崎 克也
    • Organizer
      第32回日本肥満学会
    • Place of Presentation
      淡路
    • Related Report
      2011 Research-status Report
  • [Presentation] 2 型糖尿病モデルGKラットにおける週齢特異的過食の成因2011

    • Author(s)
      安藤 明彦
    • Organizer
      第32回日本肥満学会
    • Place of Presentation
      淡路
    • Related Report
      2011 Research-status Report
  • [Presentation] Ghrelin inhibits insulin release by attenuating cAMP pathway in islet β-cells2011

    • Author(s)
      Damdindorj Boldbaatar
    • Organizer
      第32回日本肥満学会
    • Place of Presentation
      淡路
    • Related Report
      2011 Research-status Report
  • [Presentation] GHS-Rノックアウトマウスにおける糖代謝および膵β細胞インスリン分泌2011

    • Author(s)
      倉科 智行
    • Organizer
      第32回日本肥満学会
    • Place of Presentation
      淡路
    • Related Report
      2011 Research-status Report
  • [Book] 胃全摘と摂食‐ラット胃全摘モデルにおける術式と摂食の関係、術後の摂食低下とグレリン感受性の推移‐.GI Research2013

    • Author(s)
      小泉大、出崎克也、田口昌延、安田是和、矢田俊彦
    • Publisher
      先端医学社
    • Related Report
      2013 Final Research Report
  • [Book] GI Research2013

    • Author(s)
      小泉 大
    • Total Pages
      8
    • Publisher
      先端医学社
    • Related Report
      2012 Research-status Report
  • [Book] Ghrelin's novel signaling in isletβ-cells to inhibit insulin secretion and its blockade as a promising strategy to treat type 2 diabetes. Ghrelin in Health and Disease2012

    • Author(s)
      Dezaki K, Damdindorj B, Kurashina T, Yada T
    • Publisher
      Humana Press
    • Related Report
      2013 Final Research Report
  • [Book] Ghrelin in Health and Disease2012

    • Author(s)
      Katsuya Dezaki
    • Total Pages
      21
    • Publisher
      Humana Press
    • Related Report
      2012 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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