|O'connor, Pamela Mj|
Submitted to: American Journal of Physiology - Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/6/2006
Publication Date: 2/14/2006
Citation: Orellana, R.A., O'Connor, P.M.J., Bush, J.A., Suryawan, A., Thivierge, M.C. Nguyen, H.V., Fiorotto, M.L., Davis, T.A. 2006. Modulation of muscle protein synthesis by insulin is maintained during neonatal endotoxemia. American Journal Physiology - Endocrinology and Metabolism. 291(1):E159-E166. Interpretive Summary: Sepsis (a severe infection in which bacteria have entered the bloodstream or body tissues) promotes insulin resistance and reduces protein synthesis in skeletal muscle of adult. The effect of sepsis on insulin-stimulated muscle protein synthesis has not been determined in neonates (newborn). In this study we used new-born pigs (piglets) as animal model to study the effect of insulin in sepsis. To stimulate sepsis, we infused piglets with lipopolysaccharide (LPS) for 8 hours. To study the insulin effect, we maintained glucose and amino acid at fasting level. We maintained the insulin level at fasting and fed levels. The results of this study show that in fasting insulin level, sepsis causes the reduction in skeletal muscle protein synthesis but has no effect on heart muscle protein synthesis. The results also show that insulin stimulates skeletal muscle and heart muscle in both animal groups (septic and control piglets). In conclusion, the results of this study suggest that in piglets with sepsis, the ability of insulin to stimulate protein synthesis in skeletal muscle and heart muscle does not change.
Technical Abstract: 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 ug.kg(-1).h(-1)]. Glucose and amino acids were maintained at fasting levels, insulin was clamped at either fasting or fed (2 or 10 uU/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.