|Burrin, Douglas - Doug|
|Reeds, Peter - Peter|
Submitted to: American Journal of Physiology - Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/18/2001
Publication Date: 4/1/2002
Citation: Davis,T.A., Fiorotto,M.L., Beckett,P.R., Burrin,D.G., Reeds,P.J., Vann,R., Nguyen,H.V., O'Connor,P.M.J. 2002. American Journal of Physiology - Endocrinology and Metabolism. 282(4):E880-E890. Interpretive Summary: Growth and development are characterized by high rates of protein turnover that support rapid rates of protein accretion. The relative rates of protein deposition vary among tissues, with the growth rate of the skeletal musculature being amongst the highest. The efficiency with which dietary amino acids are utilized for protein deposition is high in the neonatal animal and decreases as the animal matures. This high efficiency in the neonate is enabled by an enhanced capacity for feeding to stimulate protein synthesis. The rise in protein synthesis in response to feeding and its developmental decline are more pronounced in skeletal muscle than in other tissues. In the neonatal pig, the postprandial rises in insulin and amino acids independently stimulate protein synthesis in skeletal muscle, whereas amino acids are the principal anabolic stimulus in the liver. The developmental changes in muscle protein synthesis are regulated by alterations in the expression and activity of components of the intracellular signaling pathway that controls the initiation of translation.
Technical Abstract: In neonatal pigs, the feeding-induced stimulation of protein synthesis in skeletal muscle, but not liver, can be reproduced by insulin infusion when essential amino acids and glucose are maintained at fasting levels. In the current study, 7- and 26-day-old pigs were studied during: 1) fasting, 2) hyperinsulinemic-euglycemic-euaminoacidemic clamps, 3) euinsulinemic- euglycemic-hyperaminoacidemic clamps, and 4) hyperinsulinemic-euglycemic- hyperaminoacidemic clamps. Amino acids were clamped using a new amino acid mixture enriched in nonessential amino acids. Tissue protein synthesis was measured using a flooding dose of L-[4-**3H]phenyalanine. In 7-day-old pigs, insulin infusion alone increased protein synthesis in various skeletal muscles, with equivalent contribution of myofibrillar and sarcoplasmic proteins, as well as cardiac muscle, skin, and spleen. Amino acid infusion alone increased protein synthesis in skeletal muscle, also with equivalent contribution of myofibrillar and sarcoplasmic proteins, as well as liver, pancreas, and kidney. An elevation of both insulin and amino acids did not have an additive effect. Similar qualitative results were obtained in 26-day-old pigs, but the magnitude of stimulation of protein synthesis by insulin and/or amino acids was lower. The results suggest that, in the neonate, the stimulation of protein synthesis by feeding is mediated by either amino acids or insulin in most tissues; however, the feeding-induced stimulation of protein synthesis in skeletal muscle is uniquely regulated by both insulin and amino acids.