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

• Published in: American journal of physiology: endocrinology and metabolism Vol. 288; no. 3; pp. E585 - E591
• Main Authors: Sugita, Hiroki, Kaneki, Masao, Sugita, Michiko, Yasukawa, Takashi, Yasuhara, Shingo, Martyn, J. A. Jeevendra
• Format: Journal Article
• Language: English
• Published: United States 01.03.2005
• Subjects: Animals; Blood Glucose - metabolism; Burns - metabolism; Burns - physiopathology; Glycogen Synthase Kinase 3 - metabolism; Glycogen Synthase Kinase 3 beta; Immunoblotting; Insulin - blood; Insulin - metabolism; Insulin - pharmacology; Insulin Resistance - physiology; Male; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - metabolism; Muscle, Skeletal - metabolism; Muscle, Skeletal - 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
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00321.2004

Department of Anesthesia and Critical Care, Massachusetts General Hospital, Boston; Shriners Hospital for Children, Boston; and Harvard Medical School, Boston, Massachusetts Submitted 26 July 2004 ; accepted in final form 3 November 2004 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-3 (GSK-3 ), 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-3 , 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. protein kinase B; glycogen synthase kinase-3 ; insulin resistance Address for reprint requests and other correspondence: J. A. J. Martyn, 55 Fruit St., Boston, MA 02114.