UREMIA--EFFECTS ON INSULIN BINDING & RECEPTOR FUNCTION

尿毒症是一种以肌肉蛋白质消耗和胰岛素为特征的状态 抵抗。目前尚不清楚尿毒症如何损害胰岛素的作用，但 尿毒症诱发的缺陷(S)似乎涉及绑定以外的过程 胰岛素对其受体的作用。研究葡萄糖代谢和蛋白质 周转，大鼠外周毛肌将在规定的培养液中孵化 添加D-(U-14 C)葡萄糖和D-(2-3 H)葡萄糖 胰岛素浓度。这些对胰岛素的反应将与 胰岛素受体磷酸化的配体结合和刺激 部分纯化的肌肉受体的酪氨酸激酶活性 受体存在于来自同一大鼠的肌膜小泡中。 尿毒症大鼠和对照大鼠肌肉研究的结果将是 为了更好地理解这些功能如何与生物 胰岛素的功能，反过来，他们是否受到尿毒症的影响。 因为伴发尿毒症的代谢性酸中毒似乎是 肌肉萎缩和胰岛素抵抗，平行研究将是 在接受NaHCO3饮食的尿毒症大鼠上进行，以确定酸中毒 导致尿毒症的胰岛素抵抗。最后，它的影响 将检查不同的饮食蛋白质，以评估这些干预措施是如何 影响胰岛素反应和胰岛素受体功能。

Uremia is a state characterized by muscle protein wasting and insulin resistance. It is not known how uremia impairs insulin action, but the uremia-induced defect(s) appear to involve processes other than the binding of insulin to its receptor. To study glucose metabolism and protein turnover, rat epitrochlearis muscles will be incubated in defined media supplemented with D-(U-14 C) glucose and D-(2-3 H) glucose and varying concentrations of insulin. These responses to insulin will be compared to ligand binding and stimulation of insulin receptor phosphorylation and tyrosine kinase activity from both partially purified muscle receptors and receptors present in sarcolemmal vesicles obtained from the same rats. Results from studies involving muscles of uremic and control rats will be compared to better understand how these functions related to the biologic functions of insulin and, in turn, whether they are affected by uremia. Since the metabolic acidosis accompanying uremia appears responsible for the muscle wasting and perhaps insulin resistance, parallel studies will be conducted on uremic rats receiving dietary NaHCO3 to define how acidosis contributes to the insulin resistance of uremia. Finally, the effects of varying dietary protein will be examined to assess how these interventions affect insulin response and insulin receptor function.