EFFECT OF INSULIN AND AMINO ACIDS ON STRESS INDUCED PROTEOLYSIS

皮质类固醇过量伴随着严重的损伤或创伤导致加速肌肉蛋白质分解。 增加的蛋白水解是特别危险的，因为它会导致肌肉萎缩和虚弱。高皮质醇血症的特征是肌肉蛋白质分解增加，而蛋白质合成减少或保持不变。动物模型和间接人体数据中的证据表明，肌肉氨基酸摄取受损。 因此，我们将研究蛋白质分解是介导肌肉蛋白质代谢变化的核心假设。 我们将确定急性（8小时）和4天的皮质醇治疗（6毫克/平方米/小时）对跨膜氨基酸转运的影响。 随后，我们将确定合成代谢因子（胰岛素和氨基酸）对皮质醇过量期间氨基酸转运和肌肉蛋白质代谢的影响。 稳定同位素示踪剂将用于测量正常志愿者的这些效应。

Corticosteriod excess that accompanies major injury or trauma results in an accelerated muscle protein breakdown. The increased proteolysis is especially threatening as it results in muscle wasting and debility. Hypercortisolemia is characterized by an increase in muscle protein breakdown, while protein synthesis decreases or remains unchanged. Evidence in animal models and indirect human data suggest that muscle amino acid uptake is impaired. Therefore, we will investigate the hypothesis protein breakdown is central in mediating changes in muscle protein metabolism. We will determine the effect of acute (8hr) and four days of cortisol treatment (6 mg/m2/hr) on transmembrane amino acid transport. We will subsequently determine the effect of anabolic factors (insulin and amino acid) on amino acid transport and muscle protein metabolism during cortisol excess. Stable isotope tracers will be utilized to measure these effects in normal volunteers.