KIDNEY AND INSULIN

肾脏是胰岛素新陈代谢的主要部位， 通过肾小球滤过从循环中提取激素 从肾小球后肾小管周围循环中提取。 去除的胰岛素与根尖和根尖的特定受体结合 基侧肾小管膜。过滤后的胰岛素被内化 内吞作用和完全降解。然而，它的作用是 介导内吞作用的受体，细胞内途径 胰岛素与溶酶体和溶酶外体的作用 降解过程的隔间定义不明确。 肾小管周围循环的基侧摄取也是 之后是退化，但目前还不知道 内部化是一个先决条件。事实上，与心尖部的 在细胞的一侧，基侧内吞作用是一个次要的过程。 这项研究的目的是：1)评估胰岛素的作用 介导肾脏摄取和降解的受体 胰岛素。2)确定细胞内信号转导途径的特征 顶端和基底侧方对胰岛素的摄取和降解。3) 对胰岛素降解产物进行表征，从而 进一步加深我们对肾上皮胰岛素代谢的了解。 研究将用大鼠的肾脏进行，并用 培养的负鼠肾细胞系及原代兔近端肾细胞 肾小管上皮细胞。方法论包括亚细胞 分级、电子显微镜放射自显影、细胞培养 高压液相色谱分离。 这些研究特别有意义，因为 肾脏在胰岛素代谢中的作用。新信息 将产生应该实现我们的目标的增强 对肾脏胰岛素代谢的认识。从长远来看， 从这项研究中获得的知识应该有很大的贡献 有助于我们对胰岛素代谢生理学的理解。 总而言之，特别是将成为阐明 肾脏胰岛素代谢改变的病理生理学研究 可能发生在疾病状态下。

The kidney is a major site of insulin metabolism removing the hormone from the circulation by means of glomerular filtration and by extraction from the postglomerular peritubular circulation. Insulin removed binds to specific receptors in the apical and basolateral tubular membranes. Filtered insulin is internalized by endocytosis and degraded completely. However the role of receptors in mediating endocytosis, the intracellular pathway for insulin, and the contributin of lysosomal and extralysosomal compartments to the degradative process are poorly defined. Basolateral uptake form the peritubular circulation is also followed by degradation but it is not known whether internalization is a prerequisite. Indeed in contrast to the apical side of the cell, basolateral endocytosis is a minor process. The aim of this study are; 1) To evaluate the role of insulin receptors in mediating the renal uptake and degradation of insulin. 2) To characterize the intracellular pathways involved in the apical and basolateral uptake and degradation of insulin. 3) To characterize the products of insulin degradation and thereby to further our understanding of renal epithelial insulin metabolism. Studies will be conducted with kidneys from rats, and with cultured opossum kidney cell line and primary rabbit proximal tubular epithelial cells. Methodology includes subcellular fractionation, electron microscopic autoradiography, cell culture and high pressure liquid chromatography. These studies are particularly significant because of the major role played by the kidney in insulin metabolism. New information will be generated that should achieve our objectives of enhancing the understanding of renal insulin metabolism. In the long term, knowledge gained from this study should contribute significantly to our understanding of the physiology of insulin metabolism in general and in particular will form the basis of elucidating the pathophysiology of alterations of renal insulin metabolism that may occur in disease states.