Regulation of cardiac function by insulin signaling

2013 Fiscal Year Final Research Report

• Project/Area Number: 23390214
• 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: Kansai Medical University (2012-2013); Osaka University (2011)
• Principal Investigator: SHIOJIMA Ichiro 関西医科大学, 医学部, 教授 (90376377)
• Co-Investigator(Kenkyū-buntansha): IWASAKI Masayoshi 関西医科大学, 医学部, 講師 (30548706)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Keywords: インスリン / mTOR / 心不全

Research Abstract

Insulin signaling regulates multiple cellular processes including glucose homeostasis and transcriptional/translational regulation. Our preliminary data showed that deletion of insulin receptor gene specifically in the adult heart results in impaired cardiac contractility. We therefore tried to explore the mechanistic basis for the regulation of cardiac function by insulin signaling.
We found that Akt-mTOR pathway is specifically downregulated in the heart by insulin receptor gene deletion and activation of mTOR reverses the deleterious effect of insulin receptor knockout on contractile function. Our results suggest that insulin signaling in the heart regulates contractile function through Akt-mTOR branch.

Research Products

• [Journal Article] Sca1-derived cells are a source of myocardial renewal in the murine adult heart (2013)
  • Author(s): Uchida S, De Gaspari P, Kostin S, Jenniches K, Kilic A, Izumiya Y, Shiojima I, Grosse Kreymborg K, Renz H, Walsh K, Braun T
  • Journal Title: Stem Cell Reports Volume: 1 Pages: 397-410
  • DOI: 10.1016/j.stemcr.2013.09.004
• [Journal Article] Cardiac PI3K-Akt impairs insulin-stimulated glucose uptake independent of mTORC1 and GLUT4 translocation (2013)
  • Author(s): Zhu Y, Pereira RO, O' Neill BT, Riehle C, Ilkun O, Wende AR, Rawlings TA, Zhang YC, Zhang Q, Klip A, Shiojima I, Walsh K, Abel ED
  • Journal Title: Mol Endocrinol Volume: 27 Pages: 172-84
  • DOI: 10.1210/me.2012-1210
• [Journal Article] Short-term akt activation in cardiac muscle cells improves contractile function in failing hearts (2012)
  • Author(s): Shiojima I, Schiekofer S, Schneider JG, Belisle K, Sato K, Andrassy M, Galasso G, Walsh K
  • Journal Title: Am J Pathol Volume: 181 Pages: 1969-76
  • DOI: 10.1016/j.ajpath.2012.08.020
• [Journal Article] Complement C1q activates canonical Wnt signaling and promotes aging-related phenotypes (2012)
  • Author(s): Naito AT, Sumida T, Nomura S, Liu ML, Higo T, Nakagawa A, Okada K, Sakai T, Hashimoto A, Hara Y, Shimizu I, Zhu W, Toko H, Katada A, Akazawa H, Oka T, Lee JK, Minamino T, Nagai T, Walsh K, Kikuchi A, Matsumoto M, Botto M, Shiojima I, Komuro I
  • Journal Title: Cell Volume: 149 Pages: 1298-313
  • DOI: 10.1016/j.cell.2012.03.047
• [Journal Article] Agonist-independent constitutive activity of angiotensin II receptor promotes cardiac remodeling in mice (2012)
  • Author(s): Yasuda N, Akazawa H, Ito K, Shimizu I, Kudo-Sakamoto Y, Yabumoto C, Yano M, Yamamoto R, Ozasa Y, Minamino T, Naito AT, Oka T, Shiojima I, Tamura K, Umemura S, Paradis P, Nemer M, Komuro I
  • Journal Title: Hypertension Volume: 59 Pages: 627-33
  • DOI: 10.1016/j.stemcr.2013.09.004
• [Journal Article] Ryanodine receptor type 2 is required for the development of pressure overload-induced cardiac hypertrophy (2011)
  • Author(s): Zou Y, Liang Y, Gong H, Zhou N, Ma H, Guan A, Sun A, Wang P, Niu Y, Jiang H, Takano H, Toko H, Yao A, Takeshima H, Akazawa H, Shiojima I, Wang Y, Komuro I, Ge J
  • Journal Title: Hypertension Volume: 58 Pages: 1099-110
  • DOI: 10.1161/HYPERTENSIONAHA.111.173500
• [Presentation] 心臓インスリンシグナルによる心機能調節 (2012)
  • Author(s): 塩島一朗
  • Organizer: 日本臨床分子医学会
  • Place of Presentation: 京都
  • Year and Date: 2012-04-14