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Title: AMINO ACIDS DO NOT ALTER THE INSULIN-INDUCED ACTIVATION OF THE INSULIN SIGNALING PATHWAY IN NEONATAL PIGS

Author
item SURYAWAN, AGUS - BAYLOR COLL OF MEDICINE
item O'CONNOR, PAMELA - BAYLOR COLL OF MEDICINE
item KIMBALL, SCOT - PENN STATE UNIV
item BUSH, JILL - BAYLOR COLL OF MEDICINE
item NGUYEN, HANH - BAYLOR COLL OF MEDICINE
item JEFFERSON, LEONARD - PENN STATE UNIV
item Davis, Teresa

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/13/2003
Publication Date: 1/2/2004
Citation: Suryawan, A., O'Connor, P.M., Kimball, S.R., Bush, J.A., Nguyen, H.V., Jefferson, L.S., Davis, T.A. 2004. Amino acids do not alter the insulin-induced activation of the insulin signaling pathway in neonatal pigs. Journal of Nutrition. 134(1)24-30.

Interpretive Summary: Newborns grow rapidly because they synthesize proteins at a high rate after they eat. Muscles grow faster than liver because the increase in protein synthesis after eating is greater in muscle than in liver. The increase in protein synthesis is mediated by the rise in amino acids and insulin. We wished to identify the intracellular signaling proteins in muscle and liver that respond to the rise in amino acids and insulin. We used newborn pigs as a model for the newborn human. We found that all of the intracellular signaling proteins that we examined in muscle responded to the rise in insulin and some responded to amino acids. Not all signaling proteins we tested in liver responded to insulin or to amino acids. These study findings in baby pigs provide valuable information to enhance our scientific understanding of the mechanisms that regulate growth in newborn infants, and how we might be able to optimize infant nutrition to improve growth and development.

Technical Abstract: 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.