Submitted to: Journal of Animal Science
Publication Type: Abstract Only
Publication Acceptance Date: 4/27/2007
Publication Date: 7/8/2007
Citation: Suryawan, A., Orellana, R.A., Jeyapalan, A.S., Nguyen, H.V., Fleming, J.R., Davis, T.A. 2007. The activation of insulin and nutrient signaling components leading to translation initiation in skeletal muscle of neonatal pigs is developmentally regulated [abstract]. Journal of Animal Science, Proceeding of the 2007 Annual Meeting of the American Society of Animal Science, July 8-12, 2007, San Antonio, Texas. 85(Suppl 1):463, p. 391. Interpretive Summary:
Technical Abstract: Insulin (INS) and amino acids (AA) act independently to stimulate protein synthesis in skeletal muscle of neonatal pigs, and the responses decrease with development. The purpose of this study was to compare the effect of INS and AA on the activation of signaling components leading to translation initiation and how these responses change with development. To examine the independent role of INS, hyperinsulinemic-euglycemic-euaminoacidemic clamps were performed in fasted 6-d-old (n=4) and 26-d-old (n=6) pigs to raise plasma insulin from 5 (fasting level) to 30 (fed level) µU/ml while AA and glucose were maintained at fasting levels. To elucidate the independent role of AA, a balanced AA mixture was infused into fasted 6-d-old (n=4) and 26-d-old (n=6) pigs to raise branched-chain amino acids from 500 (fasting level) to 1000 µmol/L (fed level) while INS and glucose were maintained at fasting levels. INS, but not AA, increased the phosphorylation of protein kinase B. Both INS and AA increased the phosphorylation of mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase-1, and eukaryotic initiation factor (eIF) 4E-binding protein 1 (4E-BP1) and these responses were higher in 6-d-old compared to 26-d-old pigs (P<0.05). In 6-d-old pigs, both INS and AA reduced the binding of raptor to mTOR (P<0.05). Both INS and AA decreased the binding of 4E-BP1 to eIF4E (P<0.05) and increased eIF4E binding to eIF4G (P<0.05); these effects were greater in 6-d-old than in 26-d-old pigs (P<0.05). Furthermore, neither INS, AA, nor age had any effect on the phosphorylation of eukaryotic elongation factor 2. Our results suggest that the activation of many of the insulin and nutrient signaling components leading to translation initiation is developmentally regulated and parallels the developmental decline in protein synthesis in skeletal muscle of neonatal pigs.