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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #338326
Title: Insulin modulates energy and substrate sensing and protein catabolism induced by chronic peritonitis in skeletal muscle of neonatal pigs

Author
item MANJARIN, RODRIGO - Children'S Nutrition Research Center (CNRC)
item SURYAWAN, AGUS - Children'S Nutrition Research Center (CNRC)
item KOO, SUE - Baylor College Of Medicine
item WILSON, FIONA - Baylor College Of Medicine
item NGUYEN, HANH - Children'S Nutrition Research Center (CNRC)
item DAVIS, TERESA - Children'S Nutrition Research Center (CNRC)
item ORELLANA, RENÁN - Children'S Nutrition Research Center (CNRC)

Submitted to: Pediatric Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/26/2016
Publication Date: 8/1/2016
Citation: Manjarin, R., Suryawan, A., Koo, S.J., Wilson, F.A., Nguyen, H.V., Davis, T.A., Orellana, R.A. 2016. Insulin modulates energy and substrate sensing and protein catabolism induced by chronic peritonitis in skeletal muscle of neonatal pigs. Pediatric Research. 80(5):744-752.

Interpretive Summary: Neonatal sepsis (blood poisoning) triggered by bacterial infection, can cause muscle breakdown and insulin resistance. In this study, we determined the effect of insulin on muscle breakdown in an animal model of chronic bacterial infection. To create chronic infection for 5 days, newborn pigs underwent a specific procedure called cecal ligation and puncture surgery. During the infection period, insulin was administrated and muscle protein synthesis and breakdown, and signal transduction cascades were analyzed. The results showed that during chronic infection, insulin administration increased muscle protein synthesis through the increased activation of signaling cascades of protein synthesis. Insulin also reduced the activation of signaling cascades of protein breakdown. In conclusion, the results suggest that insulin can be used to alleviate the negative effect of chronic bacterial infection on muscle breakdown. This study has potential application in the hospital to help newborn babies with chronic bacterial infection.

Technical Abstract: Acute infection promotes skeletal muscle wasting and insulin resistance, but the effect of insulin on energy and substrate sensing in skeletal muscle of chronically infected neonates has not been studied. Eighteen 2-d-old pigs underwent cecal ligation and puncture (CLP) or sham surgery (CON) to induce a chronic infection for 5 d. On d 5, pancreatic-substrate clamps were performed to attain fasting or fed insulin levels but to maintain glucose and amino acids in the fasting range. Total fractional protein synthesis rates (Ks), translational control mechanisms, and energy sensing and degradation signal activation were measured in longissimus dorsi muscle. In fasting conditions, CLP reduced Ks and sirtuin 1 (SIRT1) and increased AMP-activated protein kinase a (AMPKa) activation and muscle RING-finger protein-1 (MuRF1). Insulin treatment increased Ks and mitochondrial protein synthesis, enhanced translation activation, and reduced SIRT1 in CON. In contrast, in CLP, insulin treatment increased Ks, protein kinase B (PKB) and Forkhead box O1 phosphorylation, antagonized AMPK activation, and decreased peroxisome proliferator-activated receptor gamma coactivator 1-a (PGC-1a), MuRF1, and SIRT1. Energy and substrate sensing in skeletal muscle by the PKB-AMPK-SIRT1-PGC-1a axis is impacted by chronic infection in neonatal pigs and can be modulated by insulin.