Insulin signaling to the glomerular podocyte is critical for normal kidney function.
Insulin signaling to the glomerular podocyte is critical for normal kidney function.
复制标题
向肾小球足细胞发出的胰岛素信号对于正常肾功能至关重要。
DOI：
10.1016/j.cmet.2010.08.015
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发表时间：
2010-10-06
期刊：
影响因子：
29
通讯作者：
Coward RJM
中科院分区：
文献类型：
--
作者：
Welsh GI;Hale LJ;Eremina V;Jeansson M;Maezawa Y;Lennon R;Pons DA;Owen RJ;Satchell SC;Miles MJ;Caunt CJ;McArdle CA;Pavenstädt H;Tavaré JM;Herzenberg AM;Kahn CR;Mathieson PW;Quaggin SE;Saleem MA;Coward RJM
糖尿病肾病（diabetic nephropathy，DN）是世界范围内引起肾功能衰竭的主要原因。其特征是蛋白尿和肾小球功能异常，被认为是糖尿病的高血凝性“微血管”并发症，意味着内皮的原发性缺陷。然而，我们以前已经表明，人类足细胞对胰岛素有强烈的反应。为了确定足细胞中的胰岛素信号传导是否影响体内肾小球功能，我们产生了从足细胞特异性缺失胰岛素受体的小鼠。这些动物发生显著的白蛋白尿，并伴有概括DN的组织学特征，但处于正常血容量环境中。在体内和体外对“正常”胰岛素应答足细胞的检查表明，胰岛素通过MAPK和PI 3-激酶途径经由胰岛素受体发出信号，并直接重塑该细胞的肌动蛋白细胞骨架。总的来说，这项工作揭示了足细胞胰岛素敏感性对肾功能的至关重要性。
Diabetic nephropathy (DN) is the leading cause of renal failure in the world. It is characterized by albuminuria and abnormal glomerular function and is considered a hyperglycaemic “microvascular’ complication of diabetes, implying a primary defect in the endothelium. However, we have previously shown that human podocytes have robust responses to insulin. To determine whether insulin signaling in podocytes affects glomerular function in vivo we generated mice with specific deletion of the insulin receptor from their podocytes. These animals develop significant albuminuria together with histological features that recapitulate DN, but in a normoglycaemic environment. Examination of “normal” insulin responsive podocytes in vivo and in vitro demonstrates that insulin signals through the MAPK and PI3-kinase pathways via the insulin receptor and directly remodels the actin cytoskeleton of this cell. Collectively, this work reveals the critical importance of podocyte insulin sensitivity for kidney function.