Acute, Muscle-Type Specific Insulin Resistance Following Injury
Acute insulin resistance can develop following critical illness and severe injury, and the mortality of critically ill patients can be reduced by intensive insulin therapy. Thus, compensating for the insulin resistance in the clinical care setting is important. However, the molecular mechanisms that lead to the development of acute injury/infection-associated insulin resistance are unknown, and the development of acute insulin resistance is much less studied than chronic disease-associated insulin resistance. An animal model of injury and blood loss was utilized to determine whether acute skeletal muscle insulin resistance develops following injury, and surgical trauma in the absence of hemorrhage had little effect on insulin-mediated signaling. However, following hemorrhage, there was an almost complete loss of insulin-induced Akt phosphorylation in triceps, and severely decreased tyrosine phosphorylation of the insulin receptor and insulin receptor substrate-1. The severity of insulin resistance was similar in triceps and extensor digitorum longus muscles, but was more modest in diaphragm, and there was little change in insulin signaling in cardiac muscle following hemorrhage. Since skeletal muscle is an important insulin target tissue and accounts for much of insulin-induced glucose disposal, it is important to determine its role in injury/infection-induced hyperglycemia. This is the first report of an acute development of skeletal muscle insulin signaling defects. The presented data indicates that the defects in insulin signaling occurred rapidly, were reversible and more severe in some skeletal muscles, and did not occur in cardiac muscle.
This work is supported by grants from the National Institutes of Health (DK62071), the Department of Defense (W81XWH-0510387), and the Veterans Administration Merit Review to JLM. A University of Alabama Comprehensive Minority Faculty and Student Development Program Fellowship provided support for LHT. We would like to acknowledge the members of the University of Alabama Center for Surgical Research for vital assistance in setting up the animal model in our lab, MM Bamman and DJ Kosek for additional technical assistance, and the Metabolism Core Laboratory of the Clinical Nutrition Research Center at University of Alabama (P30-DK56336) for the serum insulin and TNF-α measurements. We also would like to thank JL Franklin, Drs. AB Keeton, and MG Schwacha, for their helpful and insightful discussions and suggestions.