L-Arginine (Arg) is synthesised from glutamine, glutamate, and proline via the intestinal-renal axis in humans and most other mammals (including pigs, sheep and rats). Arg degradation occurs via multiple pathways that are initiated by arginase, nitric-oxide synthase, Arg:glycine amidinotransferase, and Arg decarboxylase. These pathways produce nitric oxide, polyamines, proline, glutamate, creatine, and agmatine with each having enormous biological importance. Arg is also required for the detoxification of ammonia, which is an extremely toxic substance for the central nervous system. There is compelling evidence that Arg regulates interorgan metabolism of energy substrates and the function of multiple organs. The results of both experimental and clinical studies indicate that Arg is a nutritionally essential amino acid (AA) for spermatogenesis, embryonic survival, fetal and neonatal growth, as well as maintenance of vascular tone and hemodynamics. Moreover, a growing body of evidence clearly indicates that dietary supplementation or intravenous administration of Arg is beneficial in improving reproductive, cardiovascular, pulmonary, renal, gastrointestinal, liver and immune functions, as well as facilitating wound healing, enhancing insulin

The study aimed to determine the developmental changes in the response of peripheral and visceral tissue protein synthesis to feeding during early postnatal life and the associated changes in circulating insulin, insulin-like growth factor (IGF-I), and amino acid concentrations. Tissue protein synthesis was measured in vivo with a large dose of L-[4(-3)H]phenylalanine in 7- and 26-day-old pigs that were either fasted for 24 h or refed for 2.75 h after a 24-h fast. Fractional rates of protein synthesis (Ks) in skeletal muscle, heart, and liver were greater in 7-than in 26-day-old pigs. Refeeding stimulated Ks in skeletal muscle, pancreas, jejunum, and liver of both 7-and 26-day-old pigs. The stimulation of skeletal muscle and jejunal Ks by refeeding was greater in 7- than in 26-day-old pigs. Plasma IGF-I concentrations were lower in 7- than in 26-day-old pigs. Plasma concentrations of insulin and amino acids increased with refeeding. The increase in plasma insulin concentrations with refeeding was greater in 7- than in 26-days-old pigs. These results indicate that the stimulation in skeletal muscle and jejunal protein synthesis by feeding is elevated in young compared with older suckling pigs. This enhanced stimulation of protein synthesis by feeding in neonatal pigs is associated with elevated circulating concentrations of insulin but not amino acids or IGF-I.

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 present 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-(3)H]phenylalanine. In 7-day-old pigs, insulin infusion alone increased protein synthesis in various skeletal muscles (from +35 to +64%), with equivalent contribution of myofibrillar and sarcoplasmic proteins, as well as cardiac muscle (+50%), skin (+34%), and spleen (+26%). Amino acid infusion alone increased protein synthesis in skeletal muscles (from +28 to +50%), also with equivalent contribution of myofibrillar and sarcoplasmic proteins, as well as liver (+27%), pancreas (+28%), and kidney (+10%). 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 the 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.