KIDNEY AND INSULIN

肾脏是胰岛素代谢的主要部位， 通过肾小球滤过从循环中排出的激素 以及从肾小球后管周循环中提取。 去除的胰岛素与顶端的特定受体结合， 基底外侧小管膜。 过滤后的胰岛素通过以下途径内化： 内吞并完全降解。 然而， 受体介导的内吞作用，细胞内途径， 胰岛素以及溶酶体和溶酶体外 降解过程的隔室定义不明确。 从管周循环的基底外侧摄取也是 然后是降解，但不知道是否 内部化是一个先决条件。 与之相反， 在细胞的基底侧，内吞作用是一个次要过程。 本研究的目的是：1）评价胰岛素的作用 受体介导的肾脏吸收和降解的 胰岛素 2)为了表征参与的细胞内途径， 胰岛素的顶侧和基底侧摄取和降解。 第三章 表征胰岛素降解产物，从而 进一步加深了我们对肾上皮胰岛素代谢的理解。 研究将使用大鼠的肾脏进行， 培养负鼠肾细胞系和原代兔近端 肾小管上皮细胞 方法包括亚细胞 分离，电镜放射自显影，细胞培养 和高压液相色谱法。 这些研究特别重要，因为 肾脏在胰岛素代谢中的作用。 新信息 将产生的，应该实现我们的目标， 了解肾脏胰岛素代谢。 从长远来看， 从这项研究中获得的知识将大大有助于 我们对胰岛素代谢生理学的理解， 一般性的，特别是将形成阐明的基础 肾胰岛素代谢改变的病理生理学， 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.