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Title: THE REGULATORY ROLES OF INSULIN AND AMINO ACIDS IN NEONATAL LIVER PROTEIN SYNTHESIS

Author
item O'CONNOR, PAMELA - BAYLOR COLLEGE MED
item NGUYEN, HANH - BAYLOR COLLEGE MED
item SURYAWAN, AGUS - BAYLOR COLLEGE MED
item BUSH, JILL - BAYLOR COLLEGE MED
item KIMBALL, SCOT - PENN STATE COLLEGE MED
item Davis, Teresa

Submitted to: Pediatric Academic Society
Publication Type: Abstract Only
Publication Acceptance Date: 3/1/2002
Publication Date: 3/1/2002
Citation: O'Connor, P.M., Nguyen, H.V., Suryawan, A., Bush, J.A., Kimball, S.R., Davis, T.A. 2002. The regulatory roles of insulin and amino acids in neonatal liver protein synthesis [abstract]. Pediatric Research Society. Part II, 51(4):136A.

Interpretive Summary: Not needed for an Abstract

Technical Abstract: BACKGROUND: The rate of protein deposition is more rapid during the neonatal period than at any other stage of postnatal life. This high efficiency is driven by high rates of protein synthesis, which are maximally stimulated after feeding. The infusion of amino acids, but not insulin, reproduces the feeding-induced stimulation of liver protein synthesis, but whether this is independent of insulin is not clear. OBJECTIVE: This study examines the regulatory roles of insulin and amino acids, alone or in combination, in the stimulation of liver protein synthesis. DESIGN/METHODS: Insulin secretion of fasted 7-d-old pigs (n=9-12/group) was blocked with somatostatin. Insulin was then infused to achieve plasma concentrations of 0, 2, 6, and 30 uU/ml. In addition, amino acids were clamped at fasting or fed levels, and, at the high insulin dose, below fasting. Liver protein synthesis rates and liver translation initiation factor content and/or phosphorylation were determined. RESULTS: Amino acids increased liver protein synthesis by approximately 11% at the 0, 2, and 6uU/ml insulin doses and by 34% at the 30uU/ml dose (p<0.05). At the high insulin dose, there was a dose response effect of amino acids on liver protein synthesis. Amino acids increased p70S6K and 4E-BP1 phosphorylation and decreased inactive eIF4E-4E-BPI complex content; these responses were unaffected by insulin. CONCLUSIONS: The results suggest that: 1) The stimulation of liver protein synthesis by amino acids is independent of insulin in neonates; 2) Amino acids regulate liver protein synthesis in neonates by modulating the availability of eIF4E for 48S ribosomal complex formation; 3) The post-prandial rise in amino acids mediates the feeding-induced stimulation of liver protein synthesis in neonates.