Amino acids do not alter the insulin-induced activation of the insulin signaling pathway in neonatal pigs.
Feeding stimulates protein synthesis in skeletal muscle and liver of neonates and this response can be reproduced in muscle by the infusion of insulin or amino acids and in liver by the infusion of amino acids, but not insulin. Activation of insulin signaling components leading to translation initiation is associated with the feeding-induced stimulation of muscle protein synthesis in neonates. In this study, we examined the individual roles of insulin and amino acids in the activation of insulin signaling components leading to translation initiation, specifically, the insulin receptor (IR), insulin receptor substrate 1 (IRS-1), phosphatidylinositol 3-kinase (PI 3-kinase), protein kinase B (PKB) and ribosomal protein S6. Insulin secretion was blocked by somatostatin in food-deprived, 7-d-old pigs (n=8-12/group); insulin was infused to achieve plasma levels of approximately 0, 17, 52, and 255 pmol/L (approximately 0, 2, 6, 30 microU/mL), and amino acids were clamped at food-deprived or fed levels. In skeletal muscle, insulin increased the activation of IR, IRS-1, PI 3-kinase, PKB and S6 and stimulated protein synthesis. In liver, insulin increased the activation of IR, IRS-1, PI 3-kinase, PKB and S6, but had no effect on protein synthesis. Raising amino acids from the food-deprived to the fed level did not alter the insulin-induced activation of IR, IRS-1, PI 3-kinase and PKB but increased S6 phosphorylation and protein synthesis in skeletal muscle and liver. The results suggest that the stimulation of protein synthesis in muscle by insulin involves activation of insulin signaling components, and the stimulation of protein synthesis in muscle and liver by amino acids occurs by mechanisms independent of the early steps of this pathway. Furthermore, amino acids do not alter the insulin-stimulated activation of early steps in the insulin signaling pathway.
Suryawan
Agus
A
US Department of Agriculture/Agriculture Research Service, Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
O'Connor
Pamela M J
PM
Kimball
Scot R
SR
Bush
Jill A
JA
Nguyen
Hanh V
HV
Jefferson
Leonard S
LS
Davis
Teresa A
TA
D000596:Amino Acids / Q000008:administration & dosage* / Q000097:blood; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D004789:Enzyme Activation; D015309:Glucose Clamp Technique; D007163:Immunosorbent Techniques; D007328:Insulin / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology*; D055504:Insulin Receptor Substrate Proteins; D008099:Liver / Q000378:metabolism; D009124:Muscle Proteins / Q000096:biosynthesis; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D011972:Receptor, Insulin / Q000378:metabolism; D038601:Ribosomal Protein S6 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013552:Swine / Q000378:metabolism*
D000596:Amino Acids; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D009124:Muscle Proteins; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D011972:Receptor, Insulin; D038601:Ribosomal Protein S6