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Title: Insulin accelerates global and mitochondrial protein synthesis rates in neonatal muscle during sepsis

Author
item ORELLANA, RENAN - Children'S Nutrition Research Center (CNRC)
item GAZZANEO, MARIA - Children'S Nutrition Research Center (CNRC)
item WILSON, FIONA - Pennsylvania State University
item NGUYEN, HANH - Children'S Nutrition Research Center (CNRC)
item SURYAWAN, AGUS - Children'S Nutrition Research Center (CNRC)
item ALMONACI, ROSEMARY - Children'S Nutrition Research Center (CNRC)
item DAVIS, TERESA - Children'S Nutrition Research Center (CNRC)

Submitted to: Federation of American Societies for Experimental Biology Conference
Publication Type: Abstract Only
Publication Acceptance Date: 2/20/2009
Publication Date: 4/2/2009
Citation: Orellana, R.A., Gazzaneo, M.C., Wilson, F.A., Nguyen, H.V., Suryawan, A., Almonaci, R., Davis, T.A. 2009. Insulin accelerates global and mitochondrial protein synthesis rates in neonatal muscle during sepsis [abstract]. Federation of American Societies for Experimental Biology Conference: Today's Research: Tomorrow's Health. Session: Piglet model of perinatal growth, nutrition and digestive physiology, April 18-22, 2009, New Orleans, Louisiana. Electronic Abstract: 23(1) Abstract No. 33.2.

Interpretive Summary:

Technical Abstract: In neonatal pigs, sepsis decreases protein synthesis in skeletal muscle by decreasing translation initiation. However, insulin stimulates muscle protein synthesis despite persistent repression of translation initiation signaling. To determine whether the insulin-induced increase in global rates of muscle protein synthesis during neonatal sepsis involves an increase in protein synthesis in the mitochondria, neonatal pigs (n=16) underwent cecal ligation and puncture or sham surgery and were pair-gavage fed for 5 days. Pancreatic-substrate clamps were performed to achieve fasting or refed insulin levels and fractional protein synthesis rates and translational control mechanisms were examined in muscle. CLP increased IL-8 and CRP, but not TNF-alpha, and reduced weight gain. In fasted pigs, CLP reduced global and mitochondrial fractional protein synthesis in muscle. Raising insulin increased global and mitochondrial fractional muscle protein synthesis rates in sham and CLP animals, but increased eIF4G-eIF4E association in shams only. The results suggest that mitochondrial dysfunction contributes to the sepsis-associated decrease in basal protein synthesis rates in skeletal muscle, which may be ameliorated by insulin stimulation.