Regulation of cell-metabolism by cardiovascular hormones and the comprehensive application to metabolic syndrome.

• Project/Area Number: 21390286
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Keio University
• Principal Investigator: ITOH Hiroshi 慶應義塾大学, 医学部, 教授 (40252457)
• Co-Investigator(Kenkyū-buntansha): NAKAE Jun 慶應義塾大学, 医学部, 特任准教授 (00344573) ; WATANABE Mitsuhiro 慶應義塾大学, 医学部, 特任准教授 (10450842) ; SONE Masakatsu 京都大学, 大学院・医学研究科, 助教 (40437207)
• Research Collaborator: ICHIHARA Atsuhiro 東京女子医科大学, 医学部高血圧内分泌内科, 主任教授 (60203105) ; SASAMURA Hiroyuki 慶應義塾大学, 医学部, 特任准教授 (00235293) ; SHIBATA Hirotaka 慶應義塾大学, 医学部, 専任講師 (20245484) ; WAKINO Shu 慶應義塾大学, 医学部, 専任講師 (50265823) ; MIYASHITA Kazutoshi 慶應義塾大学, 医学部, 特任講師 (50378759)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000); Fiscal Year 2011: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2010: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2009: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
• Keywords: 内分泌学 / 抗加齢医学 / 細胞代謝 / 心血管ホルモン / メタボリックシンドローム / FOXO1 / 胆汁酸 / iPS細胞 / Fox01 / FoxO1

Research Abstract

Cardiovascular hormones control cytoskeletal structure in vascular smooth muscle cells and regulate vascular tonus. The present study revealed the regulation of cell-metabolism by cardiovascular hormones via modulation of intracellular organelles. The findings suggest comprehensive application of vascular hormones from the metabolic syndrome to cardiovascular diseases.

Research Products

• [Journal Article] Lowering Bile Acid Pool Size with a Synthetic Farnesoid X Receptor(FXR) Agonist Induces Obesity and Diabetes through Reduced Energy Expenditure (2011)
  • Author(s): Watanabe M, Horai Y, Houten SM, Morimoto K, Sugizaki T, Arita E, Mataki C, Sato H, Tanigawara Y, Schoonjans K, H Itoh
  • Journal Title: J Bio Chem Volume: 286(30) Pages: 26913-26920
  • Peer Reviewed
• [Journal Article] (Pro) renin receptor is essential for normal podocyte structure and function (2011)
  • Author(s): Oshima Y, Kinouchi K, Ichihara A, Sakoda M, Kurauchi-Mito A, Bokuda K, Narita T, Kurosawa H, Ge-Hong Sun-Wada, Wada Y, Yamada T, Takemoto M, Moin A. Saleem, Susan E. Quaggin, H Itoh
  • Journal Title: Journal of the American Society of Nephrology Volume: 22(12) Pages: 2203-12
  • Peer Reviewed
• [Journal Article] Rho/Rho-kinase activity in adipocytes contributes to a vicious cycle in obesity that may involve mechanical stretch (2011)
  • Author(s): Hara Y, Wakino S, Tanabe Y, Saito M, Tokuyama H, Washida N, Tatematsu S, Yoshioka K, Homma K, Hasegawa K, Minakuchi H, Fujimura K, Hosoya K, Hayashi K, Nakayama K, H Itoh
  • Journal Title: Sci Signal Volume: 4(157) Pages: 3-3
  • Peer Reviewed
• [Journal Article] Rho and Rho-kinase activity in adipocytes contributes to a vicious cycle in obesity that may involve mechanical stretch (2011)
  • Author(s): Hara Y, et al
  • Journal Title: Sci Signal Volume: 4 Issue: 157
  • DOI: 10.1126/scisignal.2001227
  • Peer Reviewed
• [Journal Article] (Pro) renin receptor is essential for normal podocyte structure and function (2011)
  • Author(s): Oshima Y, Kinouchi K, et al
  • Journal Title: J Am Soc Nephrol Volume: 22 Issue: 12 Pages: 2203-2212
  • DOI: 10.1681/asn.2011020202
  • Peer Reviewed
• [Journal Article] Lowering bile acid pool size with a synthetic farnesoid X receptor agonist induces obesity and diabetes through reduced energy expenditure (2011)
  • Author(s): Watanabe M, et al
  • Journal Title: J Biol Chem Volume: 286 Issue: 30 Pages: 26913-26920
  • DOI: 10.1074/jbc.m111.248203
  • Peer Reviewed
• [Journal Article] Rho and Rho-Kinase Activity in Adipocytes Contributes to a Vicious Cycle in Obesity That May Involve Mechanical Stretch. (2011)
  • Author(s): Y hara, et al.
  • Journal Title: Science Signaling. Volume: 4(157)ra3 Pages: 1-11
  • Peer Reviewed
• [Journal Article] The(Pro) rennin Receptor/ATP6AP2 is Essential for Vascuolar H+-ATPase Assembly in Murine Cardiomyocytes (2010)
  • Author(s): K Kinouchi, A Ichihara, M Sano, Ge-Hong Sun-Wada, Y Wada, A Kurauchi-Mito, K Bokuda, T Narita, Y Oshima, M Sakoda, Y Tamai, H Sato, K Fukuda, H Itoh
  • Journal Title: Circ Res Volume: 107 Pages: 30-34
  • Peer Reviewed
• [Journal Article] Kidney-specific Overexpression of Sirt1 Protects against Acute Kidney Injury by Retaining Peroxisome Function (2010)
  • Author(s): K. Hasegawa, S Wakino, K Yoshioka, S Tatematsu, Y Hara, H Minakuchi, K Sueyasu, N Washida, H Tokuyama, M Tzukerman, K Skorecki, K Hayashi, H Itoh
  • Journal Title: J Biol Chem Volume: 285(17) Pages: 13045-13056
  • Peer Reviewed
• [Journal Article] Sirt1 plays an important role in mediating greater functionality of human ES/iPS-derived vascular endothelial cells (2010)
  • Author(s): Homma K, Sone M, Taura D, Yamahara K, Suzuki Y, Takahashi K, Sonoyama T, Inuzuka M, Fukunaga Y, Tamura N, H Itoh, Yamanaka S, Nakao K
  • Journal Title: Atherosclerosis Volume: 212(1) Pages: 42-7
  • NAID: 120002598375
  • Peer Reviewed
• [Journal Article] Kidney-specific Overexpression of Sirt1 Protects against Acute Kidney Injury by Retaining Peroxisome Function. (2010)
  • Author(s): K Hasegawa, et al.
  • Journal Title: The Journal of Biological Chemistry. Volume: 285(17) Pages: 13045-13056
  • Peer Reviewed
• [Journal Article] The (Pro)rennin Receptor/ATP6AP2 is Essential for Vascuolar H^+-ATPase Assembly in Murine Cardiomyocytes. (2010)
  • Author(s): K Kinouchi, et al.
  • Journal Title: Circulation Research. Volume: 107 Pages: 30-34
  • Peer Reviewed
• [Journal Article] メタボリックドミノ (2010)
  • Author(s): 宮下和季, 伊藤裕, ほか
  • Journal Title: Cardio Diabetic frontier (出版準備中(出版確定))
• [Journal Article] アンジオテンシン受容体拮抗薬と2型糖尿病 (2010)
  • Author(s): 宮下和季, 伊藤裕, ほか
  • Journal Title: アンジオテンシンリサーチ 7 Pages: 1-6
• [Journal Article] (2010)
  • Author(s): 中江淳・伊藤裕
  • Journal Title: Annual Review 糖尿病・代謝・内分泌(中外医学社) Pages: 34-39
• [Journal Article] Induction and isolation of vascular cells from human induced pluripotent stem cells-brief report (2009)
  • Author(s): Taura D, Sone M, Homma K, Oyamada N, Takahashi K, Tamura N, Yamanaka S, Nakao K
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 29(7) Pages: 1100-3
  • Peer Reviewed
• [Journal Article] Pulse treatment with high-dose angiotensin blocker reverses renal arteriolar hypertrophy and regresses hypertension (2009)
  • Author(s): K. Ishiguro, K. Hayashi, H. Sasamura, Y. Sakamaki, H Itoh
  • Journal Title: Hypertension Volume: 53 Pages: 83-89
  • Peer Reviewed
• [Journal Article] Natriuretic peptides/cGMP/cGMP-dependent protein kinase cascades promote muscle mitochondrial biogenesis and prevent obesity (2009)
  • Author(s): Miyashita K, Itoh H, Tsujimoto H, Tamura N, Fukunaga Y, Sone M, Yamahara K, Taura D, Inuzuka M, Sonoyama T, Nakao K
  • Journal Title: Diabetes Volume: 58(12) Pages: 2880-92
  • Peer Reviewed
• [Journal Article] Natriuretic peptides/cGMP/cGMP dependent-protein kinase cascades promote muscle mitochondrial biogenesis and prevent obesity (2009)
  • Author(s): 宮下和季, et al.
  • Journal Title: Diabetes 58 Pages: 2880-2892
  • Peer Reviewed
• [Journal Article] Angiotensin II reduces muscle mitochondrial content and affects glycemic control (2009)
  • Author(s): 宮下和季, et al.
  • Journal Title: Diabetes 58 Pages: 710-718
  • Peer Reviewed
• [Journal Article] Induction and isolation of vascular cells from human induced pluripotent stem cells (2009)
  • Author(s): Taura D, Sone M, et al.
  • Journal Title: Arterioscler Thromb Vase Biol. 29 Pages: 1100-1103
  • Peer Reviewed
• [Journal Article] Adipogenic differentiation of human induced pluripotent stem cells : com parison with that of human embryonic stem cells (2009)
  • Author(s): Taura D, Sone M, et al.
  • Journal Title: FEBS Lett. 583 Pages: 1029-1033
  • Peer Reviewed
• [Journal Article] メタボリックシンドローム (2009)
  • Author(s): 宮下和季, 伊藤裕, ほか
  • Journal Title: 日本臨床 67増刊7 Pages: 421-426
• [Journal Article] 糖尿病発症予防に対するACEI/ARBの効果 (2009)
  • Author(s): 宮下和季, 伊藤裕, ほか
  • Journal Title: 内分泌糖尿病科 28 Pages: 321-326
• [Journal Article] ミトコンドリアと糖尿病 (2009)
  • Author(s): 三石正憲, 宮下和季, 伊藤裕, ほか
  • Journal Title: 医学のあゆみ 232 Pages: 740-745
• [Journal Article] メタボリックシンドローム (2009)
  • Author(s): 三石正憲, 宮下和季, 伊藤裕, ほか
  • Journal Title: 日本臨床 67 Pages: 321-326
• [Journal Article] 哺乳動物におけるFOXOの役割 (2009)
  • Author(s): 中江淳, 伊藤裕, ほか
  • Journal Title: 内分泌・糖尿病科 29 Pages: 570-576
• [Journal Article] インスリン作用におけるFOXO1とその活性調節 (2009)
  • Author(s): 中江淳, 伊藤裕, ほか
  • Journal Title: 糖尿病学の進歩 43 Pages: 50-55
• [Presentation] 高血圧の成因、病態、治療に関するパラダイムシフト細胞内小器官とアンジオテンシン細胞内代謝モデュレーターとしての意義 (2011)
  • Author(s): 伊藤裕
  • Organizer: 第34回日本高血圧学会
  • Place of Presentation: 宇都宮
  • Year and Date: 2011-11-25
• [Presentation] 高血圧の成因、病態、治療に関するパラダイムシフト細胞内小器官とアンジオテンシン細胞内代謝モデュレーターとしての意義 (2011)
  • Author(s): 伊藤裕, ら
  • Organizer: 第34回日本高血圧学会
  • Place of Presentation: 栃木県総合文化センター(栃木県)(招待講演)
  • Year and Date: 2011-11-25
• [Presentation] cGMP-dependent protein kinase cascades increase muscle mitochondrial content and prevent obesity and diabetes. (2011)
  • Author(s): Miyashita K, Mitsuishi M, Muraki A, Itoh H
  • Organizer: 3^<rd> International Conference on Drug Discovery & Therapy
  • Place of Presentation: Dubai
  • Year and Date: 2011-02-07
• [Presentation] AngiotensinIIによる骨格筋ミトコンドリア制御と糖脂質代謝への関与 (2010)
  • Author(s): 三石正憲, 宮下和季, 伊藤裕, ほか
  • Organizer: 第83回日本内分泌学会
  • Place of Presentation: 京都
  • Year and Date: 2010-03-25
• [Presentation] 骨格筋ミトコンドリア制御におけるレニンアンジオテンシン系とナトリウム利尿ペプチド系の拮抗関係(シンポジウム) (2010)
  • Author(s): 宮下和季, 伊藤裕, ほか
  • Organizer: 第39回日本心脈管作動物質学会
  • Place of Presentation: 名古屋
  • Year and Date: 2010-02-05
• [Presentation] ナトリウム利尿ペプチド/cGKカスケードによる骨格筋ミトコンドリア制御の抗肥満、抗糖尿病作用 (2009)
  • Author(s): 宮下和季, 伊藤裕, ほか
  • Organizer: 第11回日本心血管内分泌代謝学会
  • Place of Presentation: 大宮
  • Year and Date: 2009-10-27
• [Presentation] ヒトの肥満・摂食異常のためのモデル動物 Brain PDK1 and TSC2 KO (2009)
  • Author(s): 中江淳, 伊藤裕, ほか
  • Organizer: 第30回日本肥満医学会
  • Place of Presentation: 浜松
  • Year and Date: 2009-10-09
• [Presentation] ナトリウム利尿ペプチド/cGMP依存性プロテインキナーゼ系の抗肥満, 抗糖尿病作用と骨格筋ミトコンドリア (2009)
  • Author(s): 宮下和季, 伊藤裕, ほか
  • Organizer: 第45回高血圧疾患モデル学会
  • Place of Presentation: 東京
  • Year and Date: 2009-09-05
• [Presentation] アンジオテンシンIIの糖脂質代謝への影響と骨格筋ミトコンドリア (2009)
  • Author(s): 三石正憲, 宮下和季, 伊藤裕, ほか
  • Organizer: 第45回高血圧疾患モデル学会
  • Place of Presentation: 東京
  • Year and Date: 2009-09-04
• [Presentation] メタボリックシンドローム・CKDの未病/退行医療とレニンアンジオテンシン系(シンポジウム) (2009)
  • Author(s): 伊藤裕
  • Organizer: 第52回日本腎臓病学会
  • Place of Presentation: 横浜
  • Year and Date: 2009-06-03
• [Presentation] メタボエイジングとホルモン(シンポジウム) (2009)
  • Author(s): 伊藤裕
  • Organizer: 第9回日本抗加齢医学会
  • Place of Presentation: 東京
  • Year and Date: 2009-05-28
• [Presentation] アンジオテンシンIIによる骨格筋ミトコンドリア制御と糖脂質代謝制御 (2009)
  • Author(s): 三石正憲, 宮下和季, 伊藤裕, ほか
  • Organizer: 第52回日本糖尿病学会
  • Place of Presentation: 大阪
  • Year and Date: 2009-05-21
• [Presentation] FoxO1結合蛋白P13はCrtcの転写活性を抑制する (2009)
  • Author(s): 中江淳, 伊藤裕, ほか
  • Organizer: 第52回日本糖尿病学会
  • Place of Presentation: 大阪
  • Year and Date: 2009-05-21
• [Presentation] Angiotensin IIによる骨格筋ミトコンドリア制御と耐糖能障害 (2009)
  • Author(s): 三石正憲, 宮下和季, 伊藤裕, ほか
  • Organizer: 第46回日本臨床分子医学会
  • Place of Presentation: 東京
  • Year and Date: 2009-04-12
• [Book] 最新内分泌代謝学高血圧・血管と内分泌総論 (2012)
  • Author(s): 宮下和季、伊藤裕
  • Publisher: 診断と治療社(印刷中)
• [Book] 最新内分泌代謝学高血圧・血管と内分泌総論 (2012)
  • Author(s): 宮下和季、伊藤裕, ら
  • Publisher: 診断と治療社(印刷中)
• [Remarks]
  • URL: http://www.keio-emn.jp/
• [Remarks]
  • URL: http://www.keio-emn.jp/
• [Remarks]
  • URL: http://www.keio-emn.jp/
• [Remarks]
  • URL: http://www.keio-emn.jp/
• [Patent(Industrial Property Rights)] 慢性腎臓病判定用血清マーカーおよびその検出方法、装置 (2009)
  • Inventor(s): 篠村裕之、林香、伊藤裕、末松誠、曽我朋義
  • Industrial Property Rights Holder: 篠村裕之、林香、伊藤裕、末松誠、曽我朋義
  • Filing Date: 2009-08-17