Submitted to: Federation of American Societies for Experimental Biology Conference
Publication Type: Abstract Only
Publication Acceptance Date: 3/24/2004
Publication Date: 4/17/2004
Citation: Orellana, R.A., Kimball, S.R., Nguyen, H.V., Bush, J.A., Suryawan, A., Thivierge, M.C., Liu, W., Jefferson, L.S., Davis, T.A. 2004. Insulin stimulates muscle protein synthesis in neonates during endotoxemia despite suppression of insulin-stimulated mTOR-dependent translation initiation [abstract]. Federation of American Societies for Experimental Biology Conference. 18(5):A855.
Interpretive Summary: Not needed for an Abstract
Technical Abstract: Skeletal muscle protein synthesis is reduced in neonatal pigs in response to endotoxemia. To examine the role of insulin in this response, neonatal pigs were infused with endotoxin [LPS, 0 and 10 µg/(kg·hr)] while glucose and amino acids were maintained at fasting levels and insulin was clamped at fasting or fed (2 or 10 µU/ml) levels. Fractional rates of protein synthesis and translational control mechanisms were examined. In the presence of fasting insulin, LPS reduced muscle protein synthesis (-29%); increasing insulin to fed levels accelerated muscle protein synthesis in both groups (controls, +44%; LPS +54%). LPS increased liver protein synthesis (+27%), and increasing insulin to fed levels did not alter liver protein synthesis. In muscle, LPS reduced 4E-BP1 (-46%) and S6K1 (-78%) phosphorylation and eIF4E to eIF4G binding (-80%), and increased eIF4E to 4E-BP1 binding (+44%). Raising insulin to fed levels increased 4E-BP1 (+129%) and S6K1 (+360%) phosphorylation and eIF4E to eIF4G binding (+246%), and decreased eIF4E to 4E-BP1 binding (-32%) in muscle of control but not LPS pigs. In muscle and liver, LPS and insulin did not alter eIF2B activity. Thus, in endotoxemic neonates, the insulin responsiveness of muscle protein synthesis is maintained despite suppression of mTOR-dependent translation initiation and eIF4E availability for eIF4F assembly.