Regulation of cardiac metabolism by Akt signaling

2010 Fiscal Year Final Research Report

• Project/Area Number: 20390217
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Chiba University
• Principal Investigator: SHIOJIMA Ichiro Chiba University, 医学系研究科, 寄附講座准教授 (90376377)
• Project Period (FY): 2008 – 2010
• Keywords: Akt / 糖代謝 / 脂肪酸代謝 / 心不全

Research Abstract

Akt is a serine/threonine protein kinase that is situated downstream of PI3-kinase and regulates multiple cellular processes including cell growth and glucose metabolism. The purpose of the present study was to investigate the mechanism of metabolic regulation by Akt signaling in the heart. We found that Akt activation leads to downregulation of fatty acid oxidation and that downregulation of Akt pathway in the heart leads to contractile dysfunction. These data suggest that Akt maintains cardiac function in part through regulation of ATP synthesis in the heart.

Research Products

• [Journal Article] Wnt signaling and aging-related heart disorders. (2010)
  • Author(s): Naito AT, Shiojima I, Komuro I.
  • Journal Title: Circ Res 107 Pages: 1295-1303
  • Peer Reviewed
• [Journal Article] Promotion of CHIP-mediated p53 degradation protects the heart from ischemic injury. (2010)
  • Author(s): Naito AT, Okada S, Minamino T, Iwanaga K, Liu ML, Sumida T, Nomura S, Sahara N, Mizoroki T, Takashima A, Akazawa H, Nagai T, Shiojima I, Komuro I.
  • Journal Title: Circ Res 106 Pages: 1692-1702
  • Peer Reviewed
• [Journal Article] Excessive cardiac insulin signaling exacerbates systolic dysfunction induced by pressure overload in rodents. (2010)
  • Author(s): Shimizu I, Minamino T, Toko H, Okada S, Ikeda H, Yasuda N, Tateno K, Moriya J, Yokoyama M, Nojima A, Koh GY, Akazawa H, Shiojima I, Kahn CR, Abel ED, Komuro I.
  • Journal Title: J Clin Invest 120 Pages: 1506-1514
  • Peer Reviewed
• [Journal Article] Chronic doxorubicin cardiotoxicity is mediated by oxidative DNA damage-ATM-p53-apoptosis pathway and attenuated by pitavastatin through the inhibition of Rac1 activity. (2009)
  • Author(s): Yoshida M, Shiojima I, Ikeda H, Komuro I.
  • Journal Title: J Mol Cell Cardiol 47 Pages: 698-705
  • Peer Reviewed
• [Journal Article] Interaction of myocardial insulin receptor and IGF receptor signaling in exercise-induced cardiac hypertrophy. (2009)
  • Author(s): Ikeda H, Shiojima I, Ozasa, Y, Yoshida M, Holzenberger M, C Ronald Kahn, Kenneth Walsh, Takashi Igarashi, E Dale Abel, Issei Komuro.
  • Journal Title: J Mol Cell Cardiol 47 Pages: 664-675
  • Peer Reviewed
• [Journal Article] mTORC1 activation regulates beta-cell mass and proliferation by modulation of cyclin D2 synthesis and stability. (2009)
  • Author(s): Balcazar N, Sathyamurthy A, Elghazi L, Gould A, Weiss A, Shiojima I, Walsh K, Bernal-Mizrachi E.
  • Journal Title: J Biol Chem 284 Pages: 7832-7842
  • Peer Reviewed
• [Journal Article] IGFBP-4 is an inhibitor of canonical Wnt signalling required for cardiogenesis. (2008)
  • Author(s): Zhu W, Shiojima I, Ito Y, Li Z, Ikeda H, Yoshida M, Naito AT, Nishi J, Ueno H, Umezawa A, Minamino T, Nagai T, Kikuchi A, Asashima M, Komuro I.
  • Journal Title: Nature 454 Pages: 345-349
  • Peer Reviewed
• [Journal Article] Gremlin enhances the determined path to cardiomyogenesis. (2008)
  • Author(s): Kami D, Shiojima I, Makino H, Matsumoto K, Takahashi Y, Ishii R, Naito AT, Toyoda M, Saito H, Watanabe M, Komuro I, Umezawa A.
  • Journal Title: PLoS ONE 3 Pages: e2407
  • Peer Reviewed
• [Journal Article] A crucial role of a high mobility group protein HMGA2 in cardiogenesis. (2008)
  • Author(s): Monzen K, Ito Y, Naito AT, Kasai H, Hiroi Y, Hayashi D, Shiojima I, Yamazaki T, Miyazono K, Asashima M, Naigai R, Komuro I.
  • Journal Title: Nat Cell Biol 10 Pages: 567-574
  • Peer Reviewed