Interaction of myocardial insulin receptor and IGF receptor signaling in exercise-induced cardiac hypertrophy

Hiroyuki Ikeda, Ichiro Shiojima, Yukako Ozasa, Masashi Yoshida, Martin Holzenberger, C. Ronald Kahn, Kenneth Walsh, Takashi Igarashi, E. Dale Abel, Issei Komuro

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)


Insulin-like growth factor-1 (IGF-1) signaling has recently been implicated in the development of cardiac hypertrophy after long-term endurance training, via mechanisms that may involve energetic stress. Given the potential overlap of insulin and IGF-1 signaling we sought to determine if both signaling pathways could contribute to exercise-induced cardiac hypertrophy following shorter-term exercise training. Studies were performed in mice with cardiac-specific IGF-1 receptor (IGF1R) knockout (CIGFRKO), mice with cardiac-specific insulin receptor (IR) knockout (CIRKO), CIGFRKO mice that lacked one IR allele in cardiomyocytes (IGFR-/-IR+/-), and CIRKO mice that lacked one IGF1R allele in cardiomyocytes (IGFR+/-IR-/-). Intravenous administration of IGF-1 or 75 hours of swimming over 4 weeks increased IGF1R tyrosine phosphorylation in the heart in control and CIRKO mice but not in CIGFRKO mice. Intriguingly, IR tyrosine phosphorylation in the heart was also increased following IGF-1 administration or exercise training in control and CIGFRKO mice but not in CIRKO mice. The extent of cardiac hypertrophy following exercise training in CIGFRKO and CIRKO mice was comparable to that in control mice. In contrast, exercise-induced cardiac hypertrophy was significantly attenuated in IGFR-/-IR+/- and IGFR+/-IR-/- mice. Thus, IGF-1 and exercise activates both IGF1R and IR in the heart, and IGF1R- and IR-mediated signals may serve redundant roles in the hypertrophic responses of the heart to exercise training.

Original languageEnglish
Pages (from-to)664-675
Number of pages12
JournalJournal of Molecular and Cellular Cardiology
Issue number5
Publication statusPublished - Nov 2009
Externally publishedYes


  • Cardiac hypertrophy
  • Exercise
  • Insulin receptor
  • Insulin-like growth factor receptor
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine


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