Links between the IGF-1 signalling pathways and skeletal muscle hypertrophy in sheep

Thu Nguyen

    Research output: ThesisDoctoral Thesis

    191 Downloads (Pure)

    Abstract

    [Truncated abstract] Meat yield and product quality are important to the Australian sheep meat production industry as the country faces more and more competition from overseas imports. The Callipyge genotype in sheep is a natural mutation in chromosome 18, the mode of inheritance has been termed polar over-dominance which leads to significantly greater muscle yield. Although this genetic polymorphism has been well studied, the biochemical mechanisms responsible for the muscle hypertrophy are still not fully understood. It has been shown in many systems, that insulin-like growth factor-1 (IGF-1) is one of the effectors of skeletal muscle hypertrophy. IGF-1 is involved in both the mitogen activated protein kinase (MAPK: RAS-RAP-MEK-ERK) pathway related to cell proliferation, and the phosphatidylinositol 3-kinase PI3K/Akt1/p70S6K pathway related to cell differentiation. IGF-1 causes changes in muscle protein accretion. Recent reviews describe how IGF-1 induces hypertrophy by stimulating, PI3K/Akt1/p70S6K signalling pathway, resulting in the downstream activation of protein synthesis and inhibition of protein degradation in muscle cells. Many studies have demonstrated that IGF-1 is necessary and sufficient to induce hypertrophic growth in human and mouse skeletal muscle. Thus the role of IGF-1 signalling was investigated in primary muscle cultures of Callipyge sheep. Meat yield and product quality are important to the Australian sheep meat production industry as the country faces more and more competition from overseas imports. The Callipyge genotype in sheep is a natural mutation in chromosome 18, the mode of inheritance has been termed polar over-dominance which leads to significantly greater muscle yield. Although this genetic polymorphism has been well studied, the biochemical mechanisms responsible for the muscle hypertrophy are still not fully understood. It has been shown in many systems, that insulin-like growth factor-1 (IGF-1) is one of the effectors of
    Original languageEnglish
    QualificationDoctor of Philosophy
    Publication statusUnpublished - 2009

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