This evidence is based on the three-compartment model we have recently developed in our laboratory.[49] Quizartinib cost In physiological circumstances, rates of amino acid transport in skeletal muscle were measured and found to be different depending on the amino acid. After exercise, rates of amino acid transport are significantly increased and are associated with an increased rate of protein synthesis.[50] This evidence suggests that the intracellular free amino acids that are required for the increased rate of protein synthesis in skeletal muscle are provided by the increased rate of amino acid transport from plasma by the transmembrane amino

acid transport mechanism in the cell membranes of the skeletal muscle. Rates of amino acid transport of MK-2206 research buy skeletal muscle have been examined in burned patients.[51-53] These studies clearly demonstrated an impairment of amino acid transport in skeletal muscle in burned patients, which may partially explain the negative protein balance and loss of skeletal muscle mass in burned patients. It has been shown that increased rates of protein breakdown and protein synthesis occur at the whole-body level,[14, 54] and these alterations are attributable to the increased rates of

protein breakdown and synthesis in skeletal muscle,[51] since skeletal muscle is the largest part of the body protein store. Due to an impairment of transmembrane inward amino acid transport in burned patients, 上海皓元医药股份有限公司 free amino acid supply from plasma is decreased, despite the larger quantity of free amino acids used for the increased rate of protein synthesis. The impairment of amino acid transport could not be improved by excessive calorie intake with enteral feeding[52] or by the short-term administration of insulin. A long-term pharmacological dose of insulin combined with high-carbohydrate enteral feeding improved the rate of amino acid transport.[53] Although an impairment of amino acid transport is an important mechanism of negative

protein balance in skeletal muscle in severely burned patients, the question as to whether this mechanism can be extrapolated to other conditions of critical illness remains to be solved. Since a report by Wilmore et al.[55] demonstrated that growth hormone increased nitrogen retention in patients with thermal injuries who received adequate calories and nitrogen, multiple studies over the past 25 years have confirmed the usefulness of anabolic hormone in reducing the negative nitrogen balance associated with severe protein loss.[14, 53, 55-61] Insulin is the most important anabolic hormone and has a tremendous effect on the regulation of substrate and protein metabolism. The physiological response of amino acid and protein metabolism to insulin is well known in normal volunteers.[62-64] Insulin also improves nitrogen balance in traumatized patients.[26, 65] Furthermore, insulin also stimulates amino acid transport.