Acute, Muscle-Type Specific Insulin Resistance Following Injury

Abstract

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. with insulin resistance, skeletal muscle, adipose tissue, and liver become insulin resistant. However, it is not known which of these three main insulin target tissues become insulin resistant acutely following injury. Since skeletal muscle is a main insulin target tissue, and accounts for approximately 80% of insulin-induced glucose disposal in the human body (19), it is important to understand its role in the acute development of insulin resistance. In the current study, we utilized a rat model of surgical trauma and hemorrhage to determine the development, timing, and muscle selectivity of hemorrhage-induced skeletal muscle insulin resistance. MATERIALS AND METHODS Reagents and MaterialsAll reagents and materials were obtained from Fisher Scientific (Pittsburgh, PA, USA) or Sigma-Aldrich (St. Louis, MO, USA), unless otherwise noted. Animal Model of Surgical Trauma and HemorrhageAll procedures were carried out in accordance with the guidelines set forth in the Guide for the Care and Use of Laboratory Animals and the National Institutes of Health. The experimental protocol was approved by the Institutional Animal Care and Use Committee of the University of Alabama at Birmingham. A model of surgical trauma and hemorrhage in the rat, as previously described (6,7), was used with modifications. Briefly, male SpragueDawley rats received continuous inhalation of low levels of ...

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“…These observations suggest that Drosophila could be a useful model not only for studying aging but also obesity. Nevertheless, they do not clearly indicate whether the increase of triglycerides is attributed to insulin resistance, which is not only associated with obesity (76,77) but also with trauma.…”

“…Insulin resistance has been suggested to develop following critical illness and severe injury (76). Whether IMCL is an instigator or a marker of insulin resistance is currently a topic of debate (81).…”

Role of Tissue Macrophages in the Development of Critical Illness Diabetes

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