Abstract
Background:
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.
Methods:
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.
Results:
In fasting conditions, CLP reduced Ks and sirtuin 1 (SIRT1) and increased AMP-activated protein kinase α (AMPKα) 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-α (PGC-1α), MuRF1, and SIRT1.
Conclusion:
Energy and substrate sensing in skeletal muscle by the PKB–AMPK–SIRT1–PGC-1α axis is impacted by chronic infection in neonatal pigs and can be modulated by insulin.
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Acknowledgements
We thank Jerome Stubblefield for assistance with care of animals and Rosemarie Almonaci for technical support.
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Manjarín, R., Suryawan, A., Koo, S. et al. Insulin modulates energy and substrate sensing and protein catabolism induced by chronic peritonitis in skeletal muscle of neonatal pigs. Pediatr Res 80, 744–752 (2016). https://doi.org/10.1038/pr.2016.129
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DOI: https://doi.org/10.1038/pr.2016.129
