Journal article
Interaction of myocardial insulin receptor and IGF receptor signaling in exercise-induced cardiac hypertrophy
Journal of molecular and cellular cardiology, Vol.47(5), pp.664-675
11/2009
DOI: 10.1016/j.yjmcc.2009.08.028
PMCID: PMC4886750
PMID: 19744489
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.
Details
- Title: Subtitle
- Interaction of myocardial insulin receptor and IGF receptor signaling in exercise-induced cardiac hypertrophy
- Creators
- Hiroyuki Ikeda - Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, Chiba, JapanIchiro Shiojima - Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, Chiba, JapanYukako Ozasa - Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, Chiba, JapanMasashi Yoshida - Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, Chiba, JapanMartin Holzenberger - INSERM UMR893, Saint-Antoine Hospital, Paris, FranceC. Ronald Kahn - Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA, USAKenneth Walsh - Molecular Cardiology, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA, USATakashi Igarashi - Department of Pediatrics, University of Tokyo Graduate School of Medicine, Tokyo, JapanE. Dale Abel - Program in Molecular Medicine and Division of Endocrinology, Metabolism, and Diabetes, University of Utah School of Medicine, Salt Lake City, UT, USAIssei Komuro - Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, Chiba, Japan
- Resource Type
- Journal article
- Publication Details
- Journal of molecular and cellular cardiology, Vol.47(5), pp.664-675
- DOI
- 10.1016/j.yjmcc.2009.08.028
- PMID
- 19744489
- PMCID
- PMC4886750
- NLM abbreviation
- J Mol Cell Cardiol
- ISSN
- 0022-2828
- eISSN
- 1095-8584
- Publisher
- Elsevier Ltd
- Grant note
- DOI: 10.13039/501100001700, name: Ministry of Education, Culture, Sports, Science and Technology; DOI: 10.13039/100000002, name: National Institutes of Health, award: RO1HL070070
- Language
- English
- Date published
- 11/2009
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984025275902771
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