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 阻力 目前尚不清楚尿毒症是如何损害胰岛素作用的，但 尿毒症引起的缺陷似乎涉及结合以外的过程， 胰岛素的受体。 研究葡萄糖代谢和蛋白质 周转，大鼠上滑车肌将在限定培养基中孵育 补充有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 配体结合和胰岛素受体磷酸化的刺激， 酪氨酸激酶活性来自部分纯化的肌肉受体和 受体存在于从相同大鼠获得的肌膜囊泡中。 涉及尿毒症大鼠和对照大鼠肌肉的研究结果将在 相比之下，更好地了解这些功能如何与生物 胰岛素的功能，反过来，它们是否受到尿毒症的影响。 由于伴随尿毒症的代谢性酸中毒似乎是导致 肌肉萎缩和胰岛素抵抗，平行研究将 在接受饮食NaHCO 3的尿毒症大鼠中进行，以确定酸中毒 导致尿毒症的胰岛素抵抗。 最后，影响 不同的饮食蛋白质将被检查，以评估这些干预措施如何 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.