Insulin signaling in skeletal muscle and liver of neonatal pigs during endotoxemia

Renán A. Orellana, Agus Suryawan, Scot R. Kimball, Guoyao Wu, Hanh V. Nguyen, Leonard S. Jefferson, Teresa A. Davis

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Sepsis has been associated with tumor necrosis factor α (TNF-α) and nitric oxide (NO) overproduction, insulin resistance, and a profound suppression of muscle protein synthesis. However, lesser suppression of muscle protein synthesis in neonatal pigs occurs in response to endotoxin (LPS) when glucose and amino acids are provided. We hypothesize that the LPS-induced TNF-α and NO overproduction down-regulates insulin signaling pathway activation in neonatal pigs in the presence of fed levels of insulin, glucose, and amino acids. In skeletal muscle, inducible NOS activity was increased in response to LPS infusion, but phosphorylation of the insulin receptor, insulin receptor substrate-1 (IRS-1), p42/p44 mitogen-activated protein kinase (MAPK), and protein kinase B, the association of IRS-1 with phosphatidylinositol 3-kinase (PI 3-kinase), and constitutive NOS activity were not altered. In liver, activation of the insulin receptor, IRS-1, and PI 3-kinase were not affected by LPS, but p42 MAPK phosphorylation was increased. The absence of a down-regulation in the insulin signaling cascade in muscle despite the LPS-induced increase in TNF-α and muscle iNOS, may contribute to the near-maintenance of muscle protein synthesis rates in the presence of glucose and amino acids in LPS-infused neonatal pigs.

Original languageEnglish (US)
Pages (from-to)505-510
Number of pages6
JournalPediatric Research
Volume64
Issue number5
DOIs
StatePublished - Nov 1 2008

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Insulin Receptor Substrate Proteins
Endotoxemia
Muscle Proteins
Phosphatidylinositol 3-Kinase
Skeletal Muscle
Swine
Tumor Necrosis Factor-alpha
Mitogen-Activated Protein Kinase 1
Insulin Receptor
Insulin
Amino Acids
Glucose
Liver
Nitric Oxide
Down-Regulation
Phosphorylation
Muscles
Proto-Oncogene Proteins c-akt
Mitogen-Activated Protein Kinase Kinases
Mitogen-Activated Protein Kinases

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health

Cite this

Orellana, Renán A. ; Suryawan, Agus ; Kimball, Scot R. ; Wu, Guoyao ; Nguyen, Hanh V. ; Jefferson, Leonard S. ; Davis, Teresa A. / Insulin signaling in skeletal muscle and liver of neonatal pigs during endotoxemia. In: Pediatric Research. 2008 ; Vol. 64, No. 5. pp. 505-510.
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Insulin signaling in skeletal muscle and liver of neonatal pigs during endotoxemia. / Orellana, Renán A.; Suryawan, Agus; Kimball, Scot R.; Wu, Guoyao; Nguyen, Hanh V.; Jefferson, Leonard S.; Davis, Teresa A.

In: Pediatric Research, Vol. 64, No. 5, 01.11.2008, p. 505-510.

Research output: Contribution to journalArticle

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AU - Orellana, Renán A.

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AU - Jefferson, Leonard S.

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