Insulin ameliorates skeletal muscle degradation during sepsis in neonatal pigs

Abstract

Insulin decreases whole body protein breakdown during sepsis in adolescents, but not in adults. Neonates have higher rates of muscle deposition, protein turnover, and response to insulin than adults. To determine the effects of insulin on skeletal muscle protein degradation during sepsis, neonatal pigs (n=16) underwent cecal ligation and puncture (CLP) or sham surgery and were pair‐gavage fed for 5 days. Pancreatic‐substrate clamps were performed for 2 h providing insulin to attain fasting or fed (+Ins) insulin levels and to maintain glucose and amino acids (AA) in the fasting range. Protein synthesis (PS) and protein degradation signals were examined in longissimus dorsi. Circulating insulin and total AA did not differ between CLP and Shams, but CLP had reduced plasma BCAA and Leu than Shams. CLP+Ins had lower AA deposition rates and higher circulating 3‐methylhistidine than Shams+Ins. Compared to Shams, CLP had decreased PS and Fox03 phosphorylation and increased AMPK phosphorylation and MuRF abundance in muscle. Compared to CLP, CLP+Ins had higher PS, PKB and Fox01 phosphorylation and caspase‐3 abundance, and lower PCG‐1α mRNA expression, AMPK phosphorylation and MuRF abundance in muscle. The results suggest that insulin anatagonizes the CLP‐induced decrease in PS and suppresses proteosomal degradation signal activation in skeletal muscle of neonatal pigs. NIH AR44474, NIH AR51563, and USDA 58–6250‐6–001