Signaling pathways mediating the effects of insulin-like growth factor-I in bovine muscle satellite cells

• IGF-I stimulates bovine myoblast proliferation through both the ERK and PI3K pathways.
• PI3K mediates IGF-I stimulation of bovine myoblast proliferation through cyclin D2.
• Both the ERK and PI3K pathways mediate IGF-I-stimulated protein synthesis through p70S6K.
• IGF-I inhibits protein degradation in bovine myotubes through the PI3K/AKT/FoxO3a pathway.

The objective of this study was to identify the signaling pathways mediating the effects of IGF-I on muscle cell proliferation, protein synthesis, and protein degradation in a physiologically more relevant muscle cell model. We isolated muscle satellite cells from adult cattle and expanded them as myoblasts or induced them to form myotubes in culture. We determined the effects of IGF-I on proliferation of myoblasts and protein synthesis and degradation in myotubes in the presence or absence of specific signaling inhibitors. Our data suggest that both the MEK/ERK and PI3K/AKT pathways mediate the stimulatory effect of IGF-I on myoblast proliferation and that the PI3K/AKT pathway mediates this effect through cyclin D2. Our data also suggest that both the MEK/ERK and PI3K/AKT pathways mediate the stimulatory effect of IGF-I on protein synthesis through p70S6K and that the PI3K/AKT pathway mediates the inhibitory effect of IGF-I on protein degradation through FoxO3a.