HORMONAL REGULATION OF SKELETAL MUSCLE METABOLISM

肌肉蛋白质代谢的激素调节是一个动态的过程 这反映了在任何给定的时间，几种荷尔蒙的影响。 其中研究最多的胰岛素能抑制双前臂的蛋白质分解。 肌肉和全身蛋白质。与胰岛素不同，生长激素的作用 (GH)在调节蛋白质代谢中的作用在正常人中尚未见报道 很好的特点。因为胰岛素和生长激素都是正常所必需的 人类生长激素的增长，本身或通过IGF-1，预计将影响 肌肉蛋白质代谢。提供的初步数据演示了 局部输注生长激素刺激蛋白的急性(6小时内)效应 人类前臂骨骼肌组织的合成。基于这些结果 和申请中引用的其他实验，这些实验描述了试图 解剖生长激素、胰岛素和胰岛素样生长因子-1在调节中的作用 对人体骨骼肌和全身蛋白质代谢的影响。 描述了四组实验。第一项是检查生长激素是否 以连续或脉动的方式系统地注入产生 全身和前臂肌肉蛋白质合成的急性变化 在局部动脉输注时出现在前臂肌肉。 第二组研究考察了胰岛素和生长激素之间的相互作用。 在调节蛋白质新陈代谢方面。抑制内源性生长激素和胰岛素 分泌生长抑素使我们可以建立生长激素缺乏或 正常受试者的I型糖尿病。GH或GH的选定管理 然后，这些模型中的胰岛素允许我们探索对这些模型的反应 激素在不同的病理生理环境中。 第三组实验旨在比较IGF-1的作用 与生长激素和胰岛素的作用相同。在大鼠中，IGF-1抑制肌肉蛋白分解 像胰岛素一样，并不像生长激素那样刺激蛋白质合成。 拟议的研究旨在帮助澄清行动机制。 胰岛素-生长激素-胰岛素样生长因子三联体对人体蛋白质代谢的影响。 最后，最后一组实验考察了 细胞内信使cAMP和cGMP在介导细胞免疫应答中的作用 生长激素、胰岛素和胰岛素样生长因子-1。生长激素在体外抑制细胞内钙离子浓度升高 CGMP。生长激素的这种抑制作用与刺激 蛋白质的体外合成。拟议中的实验试图与 体内注射激素，测定cGMP和cAMP水平。

The hormonal regulation of muscle protein metabolism is a dynamic process that reflects, at any given time, the effects of several hormones. Insulin, the best studied of these, suppresses proteolysis in both forearm muscle and whole body protein. Unlike insulin, the role of growth hormone (GH) in the regulation of protein metabolism in normal man has not been well characterized. Since both insulin and GH are required for normal growth in man, GH, by itself or via IGF-1, would be expected to affect muscle protein metabolism. Preliminary data in presented demonstrating an acute (within 6 hours) effect of locally infused GH to stimulate protein synthesis by forearm skeletal muscle tissue in man. Based on these results and others cited in the application, the experiments described attempt to dissect apart the contributions of GH, insulin and IGF-1 to the regulation of skeletal muscle and whole body protein metabolism in man. Four sets of experiments are described. The first examines whether GH infused systemically in either a continuous or pulsatile fashion produces acute changes in whole body and forearm muscle protein synthesis like those seen in forearm muscle during local arterial infusion. The second set of studies examines the interaction between insulin and GH in regulating protein metabolism. Suppression of endogenous GH and insulin secretion with somatostatin allows us to develop models of GH deficiency or type I diabetes in normal subjects. Selected readministration of GH or insulin in these models then allows us to probe the responses to these hormones in different pathophysiological settings. The third group of experiments in intended to compare the effects of IGF-1 with those of GH and insulin. In rats, IGF-1 suppresses muscle proteolysis like insulin and does not stimulate protein synthesis, as GH appears to do. The proposed studies are designed to help clarify the mechanisms of action of the insulin-GH-IGF triad on protein metabolism in man. Finally, the last group of experiments looks at the role of the intracellular messengers cAMP and cGMP in the mediation of the responses to GH, insulin, and IGF-1. GH in vitro prevents the intracellular rise of cGMP. This suppressive effect of GH is associated with stimulation of protein synthesis in vitro. The proposed experiments attempt to relate in vivo hormone administration with measured levels of cGMP and cAMP.