The Critical Role of Insulin-Like Growth Factor-1 Isoforms in the Physiopathology of Skeletal Muscle

A.      Musaro; N.      Rosenthal

Abstract

The prolongation of skeletal muscle strength in aging and neuromuscular disease has been the objective of numerous studies employing a variety of approaches. To date however, efforts to prevent or attenuate age- or disease-related muscle degeneration have been largely unsuccessful. Cell-based therapies have been stalled by the difficulty in obtaining sufficient numbers of autologous myoblasts and by inefficient incorporation into host muscle. Administration of growth hormone prevents age-related loss of muscle mass, but has failed to increase muscle strength. In this context, where direct therapeutic approaches to redress the primary disease are still suboptimal, it may be more effective to focus on strategies for improving skeletal muscle function. Experimental models of muscle growth and regeneration have implicated Insulin-like Growth Factor-1 (IGF-1) as an important mediator of anabolic pathways in skeletal muscle cells. Two major IGF-1 transcripts are characterized: the locally acting isoform with an autocrine/paracrine action and the circulating isoform with endocrine effects. The physiological differences between the function of local and circulating isoform of IGF-1 are not completely established. However the selective expression of the muscle-specific IGF-1 isoform avoids hypertrophic effects on distal organs such as the heart, and eliminates risk of possible neoplasms induced by inappropriate high expression levels of circulating IGF-1. In this review we discuss the roles of IGF-1 isoforms in myogenesis and the potential therapeutic role of local IGF-1 isoform on muscle aging and diseases.

Keywords: mechano growth factor, post-translational modification, cortical neurons, cartilage homeostasis, myosin light chain (MLC), myofiber

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