Invited Review: Role of Insulin in Translational Control of Protein Synthesis in Skeletal Muscle by Amino Acids or Exercise

Protein synthesis in skeletal muscle is modulated in response to a variety of stimuli. Two stimuli receiving a great deal of recent attention are increased amino acid availability and exercise. Both of these effectors stimulate protein synthesis in part through activation of translation initiation. However, the full response of translation initiation and protein synthesis to either effector is not observed in the absence of a minimal concentration of insulin. The combination of insulin and either increased amino acid availability or endurance exercise stimulates translation initiation and protein synthesis in part through activation of the ribosomal protein S6 protein kinase S6K1 as well as through enhanced association of eukaryotic initiation factor eIF4G with eIF4E, an event that promotes binding of mRNA to the ribosome. In contrast, insulin in combination with resistance exercise stimulates translation initiation and protein synthesis through enhanced activity of a guanine nucleotide exchange protein referred to as eIF2B. In both cases, the amount of insulin required for the effects is low, and a concentration of the hormone that approximates that observed in fasting animals is sufficient for maximal stimulation. This review summarizes the results of a number of recent studies that have helped to establish our present understanding of the interactions of insulin, amino acids, and exercise in the regulation of protein synthesis in skeletal muscle.