| Interaction of myocardial insulin receptor and IGF receptor signaling in exercise-induced cardiac hypertrophy. | |
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MedLine Citation:
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PMID: 19744489 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Hiroyuki Ikeda; Ichiro Shiojima; Yukako Ozasa; Masashi Yoshida; Martin Holzenberger; C Ronald Kahn; Kenneth Walsh; Takashi Igarashi; E Dale Abel; Issei Komuro |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-09-08 |
Journal Detail:
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Title: Journal of molecular and cellular cardiology Volume: 47 ISSN: 1095-8584 ISO Abbreviation: J. Mol. Cell. Cardiol. Publication Date: 2009 Nov |
Date Detail:
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Created Date: 2009-10-13 Completed Date: 2009-12-24 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0262322 Medline TA: J Mol Cell Cardiol Country: England |
Other Details:
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Languages: eng Pagination: 664-75 Citation Subset: IM |
Affiliation:
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Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, Chiba, Japan. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blotting, Western Cardiomegaly / chemically induced*, etiology*, metabolism Immunoprecipitation Insulin-Like Growth Factor I / pharmacology Male Mice Mice, Knockout Mice, Transgenic Myocardium / metabolism Phosphorylation / drug effects Physical Conditioning, Animal / physiology* Receptor, IGF Type 1 / genetics, physiology Receptor, Insulin / genetics, metabolism, physiology* Receptors, Somatomedin / genetics, physiology* |
| Grant Support | |
ID/Acronym/Agency:
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R01HL070070/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Receptors, Somatomedin; 67763-96-6/Insulin-Like Growth Factor I; EC 2.7.10.1/Receptor, IGF Type 1; EC 2.7.10.1/Receptor, Insulin |
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