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Modulation of muscle protein synthesis by insulin is maintained during neonatal endotoxemia

¹United States Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center and Sections of ²Critical Care and ³Neonatology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas; ⁴Our Lady's Hospital for Sick Children, Crumlin, Dublin, Ireland; ⁵University of Houston, Houston, Texas; and ⁶University of Laval, Sainte-Foy, Quebec, Canada

Submitted 30 November 2005 ; accepted in final form 6 February 2006

Sepsis promotes insulin resistance and reduces protein synthesis in skeletal muscle of adults. The effect of sepsis on insulin-stimulated muscle protein synthesis has not been determined in neonates, a highly anabolic population that is uniquely sensitive to insulin. Overnight fasted neonatal pigs were infused for 8 h with endotoxin [lipopolysaccharide (LPS), 0 and 10 µg·kg^–1·h^–1]. Glucose and amino acids were maintained at fasting levels, insulin was clamped at either fasting or fed (2 or 10 µU/ml) levels, and fractional protein synthesis rates were determined at the end of the infusion. LPS infusion induced a septic-like state, as indicated by a sustained elevation in body temperature, heart rate, and cortisol. At fasting insulin levels, LPS reduced fractional protein synthesis rates in gastrocnemius muscle (–26%) but had no effect on the masseter and heart. By contrast, LPS stimulated liver protein synthesis (+28%). Increasing insulin to fed levels accelerated protein synthesis rates in gastrocnemius (controls by +38%, LPS by +60%), masseter (controls by +50%, LPS by +43%), heart (controls by +34%, LPS by +40%), and diaphragm (controls by +54%, LPS by +29%), and the response to insulin was similar in LPS and controls. Insulin did not alter protein synthesis in liver, kidney, or jejunum in either group. These findings suggest that acute endotoxemia lowers basal fasting muscle protein synthesis in neonates but does not alter the response of protein synthesis to insulin.

growth; amino acids; protein metabolism; insulin resistance; sepsis

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