Insulin and amino acids independently stimulate skeletal muscle protein synthesis in neonatal pigs.
Infusion of physiological levels of insulin and/or amino acids reproduces the feeding-induced stimulation of muscle protein synthesis in neonates. To determine whether insulin and amino acids independently stimulate skeletal muscle protein synthesis in neonates, insulin secretion was blocked with somatostatin in fasted 7-day-old pigs (n = 8-12/group) while glucose and glucagon were maintained at fasting levels and insulin was infused to simulate either less than fasting, fasting, intermediate, or fed insulin levels. At each dose of insulin, amino acids were clamped at either the fasting or fed level; at the highest insulin dose, amino acids were also reduced to less than fasting levels. Skeletal muscle protein synthesis was measured using a flooding dose of l-[4-(3)H]phenylalanine. Hyperinsulinemia increased protein synthesis in skeletal muscle during hypoaminoacidemia and euaminoacidemia. Hyperaminoacidemia increased muscle protein synthesis during hypoinsulinemia and euinsulinemia. There was a dose-response effect of both insulin and amino acids on muscle protein synthesis. At each insulin dose, hyperaminoacidemia increased muscle protein synthesis. The effects of insulin and amino acids on muscle protein synthesis were largely additive until maximal rates of protein synthesis were achieved. Amino acids enhanced basal protein synthesis rates but did not enhance the sensitivity or responsiveness of muscle protein synthesis to insulin. The results suggest that insulin and amino acids independently stimulate protein synthesis in skeletal muscle of the neonate.
O'Connor
Pamela M J
PM
United States Department of Agriculture, Agricultural Research Service, Children's Nutrition Research Center and Section of Neonatology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.
Bush
Jill A
JA
Suryawan
Agus
A
Nguyen
Hanh V
HV
Davis
Teresa A
TA
D000596:Amino Acids / Q000097:blood / Q000494:pharmacology*; D000597:Amino Acids, Branched-Chain / Q000097:blood; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D004347:Drug Interactions; D005215:Fasting; D005502:Food; D007328:Insulin / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D000078790:Insulin Secretion; D007700:Kinetics; D009124:Muscle Proteins / Q000096:biosynthesis*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D010649:Phenylalanine / Q000008:administration & dosage; D013004:Somatostatin / Q000494:pharmacology; D013552:Swine / Q000378:metabolism*; D014316:Tritium
D000596:Amino Acids; D000597:Amino Acids, Branched-Chain; D007328:Insulin; D009124:Muscle Proteins; D014316:Tritium; D010649:Phenylalanine; D013004:Somatostatin