Thrailkill Kathryn M, Nimmo Teresa, Bunn R Clay, Cockrell Gael E, Moreau Cynthia S, Mackintosh Samuel, Edmondson Ricky D, Fowlkes John L
Department of Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children's Hospital Research Institute, Little Rock, Arkansas, USA.
Diabetes Care. 2009 Jul;32(7):1266-8. doi: 10.2337/dc09-0112. Epub 2009 Apr 14.
Proteinuria is the hallmark of diabetic nephropathy; yet, glomerular histology does not fully explain mechanisms contributing to proteinuria. Our objective was to identify proteins in the urine of individuals with type 1 diabetes and microalbuminuria that might implicate a mechanistic pathway operative in proteinuria.
Using a GeLC/MS platform proteomics approach, we compared the urine proteome from 12 healthy nondiabetic individuals, 12 subjects with type 1 diabetes yet normal urinary albumin excretion rates, and 12 subjects with type 1 diabetes and microalbuminuria (type 1 diabetes + microalbuminuria).
The abundance of megalin and cubilin, two multiligand receptors expressed in kidney proximal tubule cells and involved with the reuptake of filtered albumin and megalin/cubilin ligands, was significantly increased in type 1 diabetes + microalbuminuria urine, compared with both nonalbuminuric groups.
Aberrant shedding of megalin and cubilin could contribute to albuminuria in diabetes and to deficiency states of important vitamins and hormones.
蛋白尿是糖尿病肾病的标志；然而，肾小球组织学并不能完全解释导致蛋白尿的机制。我们的目的是鉴定1型糖尿病和微量白蛋白尿患者尿液中的蛋白质，这些蛋白质可能涉及蛋白尿发生的机制途径。
采用凝胶液相色谱/质谱联用（GeLC/MS）平台蛋白质组学方法，我们比较了12名健康非糖尿病个体、12名1型糖尿病但尿白蛋白排泄率正常的受试者以及12名1型糖尿病合并微量白蛋白尿（1型糖尿病+微量白蛋白尿）受试者的尿蛋白质组。
与两个无蛋白尿组相比，在1型糖尿病+微量白蛋白尿患者的尿液中，巨膜蛋白和立方蛋白（两种在肾近端小管细胞中表达的多配体受体，参与滤过白蛋白和巨膜蛋白/立方蛋白配体的重吸收）的丰度显著增加。
巨膜蛋白和立方蛋白的异常脱落可能导致糖尿病患者出现蛋白尿以及重要维生素和激素的缺乏状态。
