Expression of IGF-1 isoforms after exercise-induced muscle damage in humans: characterization of the MGF E peptide actions in vitro.

Different insulin-like growth factor-1 (IGF-1) isoforms, namely IGF-1Ea, IGF-1Eb and IGF-1Ec (MGF), have been proposed to have various functions in muscle repair and growth. To gain insight into the potentially differential actions of IGF-1 isoforms in the regulation of muscle regeneration, we assessed the time course of their expressions at both mRNA and protein levels after exercise-induced muscle damage in humans. In addition, we characterized mature IGF-1 and synthetic MGF E peptide signalling in C2C12 myoblast-like cells in vitro. Ten healthy male volunteers were subjected to exercise-induced muscle damage and biopsy samples were taken from the exercised muscles before and 6 h, 2, 5 and 16 days post exercise. Muscle damage was documented by specific functional and biochemical responses post exercise. PCR-based analyses of muscle biopsy samples revealed a rapid and transient up-regulation of MGF mRNA expression which was followed by a prolonged increase of IGF-1Ea and IGF-1Eb mRNA expression (p<0.05). Patterns similar to those for mRNA expression were detected for MGF and IGF-1Ea expression at the protein level. The action of synthetic MGF E peptide differed from that of mature IGF-1 since its proliferative effect on C2C12 myoblast-like cells was not blocked by an anti-IGF-1 receptor neutralizing antibody and it did not phosphorylate Akt. Therefore, we conclude that the differential expression profile of IGF-1 isoforms in vivo and the possible IGF-1R - independent MGF E peptide signalling in skeletal muscle-like cells in vitro support the notion that tissue-specific mRNA expression of MGF isoform produces mature IGF-1 and MGF E peptides which possibly act as distinct mitogens in skeletal muscle regeneration.