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Unlike the cells of many tissues, muscle and neuronal cells do not replicate throughout life. Therefore there has to be an effective mechanism of inducing local repair and preventing cell death. We have identified and cloned two growth factors that are expressed by muscle when it is subjected to activity which are derived from the insulin like growth factor-I (IGF-I) gene by alternative splicing.1, 2 One isoform, muscle L.IGF-I, is very similar to the liver type of IGF-I. The other is a new growth factor that could only be detected in exercised or stretched muscle. This has been called mechano growth factor (MGF) to distinguish it from liver IGF-I which has a systemic mode of action. The structure of the cDNA of this isoform indicates that it has different exons from the liver types and is not glycosylated.1 Therefore it is smaller and has a shorter half life than liver IGF-I unless it is bound to its tissue binding protein. Unlike hormones, the site and mode of action of growth factors are determined to a large extent by their specific binding proteins.
Both muscle isoforms are upregulated by stretch and overload and the evidence indicates that, during exercise, muscle L.IGF-I contributes significantly to circulating levels of IGF-I.2, 3 MGF, …