Submitted to: American Journal of Physiology - Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/2/2008
Publication Date: 5/6/2008
Publication URL: http:////ajpendo.physiology.org/cgi/reprint/295/1/E187
Citation: Wilson, F.A., Orellana, R.A., Suryawan, A., Nguyen, H.V., Jeyapalan, A.S., Frank, J., Davis, T.A. 2008. Stimulation of muscle protein synthesis by somatotropin in pigs is independent of the somatotropin-induced increase in circulating insulin. American Journal of Physiology - Endocrinology and Metabolism. 295(1):E187-E194. Interpretive Summary: Administration of somatotropin, also known as growth hormone, stimulates growth by increasing the amount of protein in the body rather than by increasing fat. We have previously shown that somatotropin treatment increases the growth of skeletal muscle by increasing the synthesis of proteins in skeletal muscle, but the mechanism by which this occurs was not identified previously. Somatotropin administration also increases the circulating concentration of the hormone insulin, which is a known promoter of the synthesis of skeletal muscle proteins. Therefore, in this study we tested the hypothesis that the mechanism by which somatotropin increases the synthesis of muscle proteins is by increasing the circulating concentration of insulin, and we examined the molecules within the muscle that regulate the synthesis of proteins. We used a special technique, which we developed, to allow us to control the circulating levels of hormones, glucose, and amino acids in the blood, while we measured the synthesis of skeletal muscle proteins. We found that somatotropin treatment increase the synthesis of skeletal muscle proteins, but the mechanism by which this occurs does not involve the hormone insulin. We also identified the molecules within the cell that signal to the protein synthetic machinery that the synthesis of skeletal muscle proteins should be increased in response to somatotropin treatment. These studies are of importance to our understanding of the regulation of growth as well as to our development of a means to increase muscle mass in farm animals.
Technical Abstract: Chronic treatment of growing pigs with porcine somatotropin (pST) promotes protein synthesis and doubles postprandial levels of insulin, a hormone that stimulates translation initiation. This study aimed to determine whether the pST-induced increase in skeletal muscle protein synthesis was mediated through an insulin-induced stimulation of translation initiation. After 7–10 days of pST (150 µg·kg(–1)·day(–1)) or control saline treatment, pancreatic glucose-amino acid clamps were performed in overnight-fasted pigs to reproduce 1) fasted (5 µU/ml), 2) fed control (25 µU/ml), and 3) fed pST-treated (50 µU/ml) insulin levels while glucose and amino acids were maintained at baseline fasting levels. Fractional protein synthesis rates and indexes of translation initiation were examined in skeletal muscle. Effectiveness of pST treatment was confirmed by reduced urea nitrogen and elevated insulin-like growth factor I levels in plasma. Skeletal muscle protein synthesis was independently increased by both insulin and pST. Insulin increased the phosphorylation of protein kinase B and the downstream effectors of the mammalian target of rapamycin, ribosomal protein S6 kinase, and eukaryotic initiation factor (eIF)4E-binding protein-1 (4E-BP1). Furthermore, insulin reduced inactive 4E-BP1·eIF4E complex association and increased active eIF4E·eIF4G complex formation, indicating enhanced eIF4F complex assembly. However, pST treatment did not alter translation initiation factor activation. We conclude that the pST-induced stimulation of skeletal muscle protein synthesis in growing pigs is independent of the insulin-associated activation of translation initiation.