title: Interaction of myocardial insulin receptor and IGF receptor signaling in exercise-induced cardiac hypertrophy.
abstract: 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.
authors.affiliation: Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ikeda
authors.forename: Ichiro
authors.initials: I
authors.lastname: Shiojima
authors.forename: Yukako
authors.initials: Y
authors.lastname: Ozasa
authors.forename: Masashi
authors.initials: M
authors.lastname: Yoshida
authors.forename: Martin
authors.initials: M
authors.lastname: Holzenberger
authors.forename: C Ronald
authors.initials: CR
authors.lastname: Kahn
authors.forename: Kenneth
authors.initials: K
authors.lastname: Walsh
authors.forename: Takashi
authors.initials: T
authors.lastname: Igarashi
authors.forename: E Dale
authors.initials: ED
authors.lastname: Abel
authors.forename: Issei
authors.initials: I
authors.lastname: Komuro
mesh_terms: D000818:Animals; D015153:Blotting, Western; D006332:Cardiomegaly / Q000139:chemically induced* / Q000209:etiology* / Q000378:metabolism; D047468:Immunoprecipitation; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010805:Physical Conditioning, Animal / Q000502:physiology*; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000502:physiology; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017451:Receptors, Somatomedin / Q000235:genetics / Q000502:physiology*
chemical_list: D017451:Receptors, Somatomedin; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin