Burn injury impairs insulin-stimulated Akt/PKB activation in skeletal muscle.

Abstract

The molecular bases underlying burn- or critical illness-induced insulin resistance still remain unclarified. Muscle protein catabolism is a ubiquitous feature of critical illness. Akt/PKB plays a central role in the metabolic actions of insulin and is a pivotal regulator of hypertrophy and atrophy of skeletal muscle. We therefore examined the effects of burn injury on insulin-stimulated Akt/PKB activation in skeletal muscle. Insulin-stimulated phosphorylation of Akt/PKB was significantly attenuated in burned compared with sham-burned rats. Insulin-stimulated Akt/PKB kinase activity, as judged by immune complex kinase assay and phosphorylation status of the endogenous substrate of Akt/PKB, glycogen synthase kinase-3beta (GSK-3beta), was significantly impaired in burned rats. Furthermore, insulin consistently failed to increase the phosphorylation of p70 S6 kinase, another downstream effector of Akt/PKB, in rats with burn injury, whereas phosphorylation of p70 S6 kinase was increased by insulin in controls. The protein expression of Akt/PKB, GSK-3beta, and p70 S6 kinase was unaltered by burn injury. However, insulin-stimulated activation of ERK, a signaling pathway parallel to Akt/PKB, was not affected by burn injury. These results demonstrate that burn injury impairs insulin-stimulated Akt/PKB activation in skeletal muscle and suggest that attenuated Akt/PKB activation may be involved in deranged metabolism and muscle wasting observed after burn injury.

• Authors: Hiroki Sugita, Masao Kaneki, Michiko Sugita, Takashi Yasukawa, Shingo Yasuhara, J A Jeevendra Martyn
• Journal: American journal of physiology. Endocrinology and metabolism (Am J Physiol Endocrinol Metab) Vol. 288 Issue 3 Pg. E585-91 (Mar 2005) ISSN: 0193-1849 [Print] United States
• PMID: 15536206 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Blood Glucose
• Insulin
• Proto-Oncogene Proteins
• Threonine
• Serine
• Akt1 protein, rat
• Glycogen Synthase Kinase 3 beta
• Gsk3b protein, rat
• Protein Serine-Threonine Kinases
• Proto-Oncogene Proteins c-akt
• Ribosomal Protein S6 Kinases, 70-kDa
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• Glycogen Synthase Kinase 3

Topics

• Animals
• Blood Glucose (metabolism)
• Burns (metabolism, physiopathology)
• Glycogen Synthase Kinase 3 (metabolism)
• Glycogen Synthase Kinase 3 beta
• Immunoblotting
• Insulin (blood, metabolism, pharmacology)
• Insulin Resistance (physiology)
• Male
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 3 (metabolism)
• Muscle, Skeletal (metabolism, physiopathology)
• Phosphorylation (drug effects)
• Protein Serine-Threonine Kinases (metabolism)
• Proto-Oncogene Proteins (metabolism)
• Proto-Oncogene Proteins c-akt
• Rats
• Rats, Sprague-Dawley
• Ribosomal Protein S6 Kinases, 70-kDa (metabolism)
• Serine (metabolism)
• Threonine (metabolism)