Albuminuria in patients with type 1 diabetes is directly linked to changes in the lysosome-mediated degradation of albumin during renal passage
Albuminuria in patients with type 1 diabetes is directly linked to changes in the lysosome-mediated degradation of albumin during renal passage
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DOI：
10.2337/diabetes.49.9.1579
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发表时间：
2000-09-01
期刊：
影响因子：
7.7
通讯作者：
Comper, WD
中科院分区：
文献类型：
--
作者：
Osicka, TM;Houlihan, CA;Comper, WD
我们小组先前的研究表明，白蛋白在啮齿动物中在肾通道中代谢，并以完整蛋白和白蛋白衍生片段的混合物形式在尿液中排泄。本研究的目的是检查白蛋白在非糖尿病志愿者和具有不同水平白蛋白尿的1型糖尿病患者中是否在肾通道中代谢，研究了9名非糖尿病正常白蛋白尿志愿者和11名1型糖尿病患者，其白蛋白排泄率从正常白蛋白尿到大量白蛋白尿不等。每例受试者静脉注射氚标记白蛋白（[H-3]-albumin），分别于注射后4 h和24 h采集尿液，用体积排阻色谱法分析。对完整和片段化白蛋白的量进行定量，并通过放射免疫测定法（RIA）分析各组分中的白蛋白。非糖尿病志愿者中的[H-3]-白蛋白在肾脏通过过程中代谢为常规RIA无法检测到的小肽片段（仅0.05-3.8%的总尿液放射性与完整白蛋白相关）。在正常白蛋白尿的糖尿病患者中，白蛋白碎片化的过程相似（完整白蛋白占总尿放射性的0.01-4.0%）。然而，在伴有微量或大量白蛋白尿的糖尿病患者中，碎片比率（碎片：完整）降低（完整白蛋白占2.7- 55.5%，P = 0.048），碎片比率的这种变化与白蛋白尿的程度直接相关。这些结果对于了解非糖尿病志愿者和I型糖尿病患者蛋白尿的机制具有重要意义。在非糖尿病志愿者中，白蛋白的肾脏处理涉及白蛋白相对快速和全面的降解为小片段（范围1-15 kDa），在糖尿病肾病中，降解过程与RIA检测到的白蛋白尿水平成比例地受到抑制。
Previous studies by our group have shown that albumin is metabolized in rodents during renal passage and excreted in the urine as a mixture of intact protein and albumin-derived fragments, The aim of this study was to examine whether albumin is metabolized during renal passage in nondiabetic volunteers and in type 1 diabetic patients with varying levels of albuminuria, Nine nondiabetic normoalbuminuric volunteers and 11 type 1 diabetic patients with albumin excretion rates varying from normoalbuminuria to macroalbuminuria were studied. Each subject received an intravenous injection of tritium-labeled albumin ([H-3]-albumin), Urine was collected at 4 h and 24 h after injection and analyzed by size exclusion chromatography. The amount of intact and fragmented albumin was quantified, and each fraction was analyzed by radioimmunoassay (RIA) for albumin, [H-3]-albumin in nondiabetic volunteers was metabolized during renal passage to small peptide fragments not detectable by conventional RIA (only 0.05-3.8% of the total urinary radioactivity was associated with intact albumin). The process responsible for albumin fragmentation was similar in diabetic patients with normoalbuminuria (intact albumin represented 0.01-4.0% of total urinary radioactivity). However, there was a reduction in the fragmentation ratio (fragmented:intact) in diabetic patients with micro- or macroalbuminuria (intact albumin represented 2.7-55.5%, P = 0.048), This change in the fragmentation ratio was directly related to the degree of albuminuria. These results have important implications for understanding the mechanisms underlying albuminuria in nondiabetic volunteers and type I diabetic patients. In nondiabetic volunteers, the renal processing of albumin involves a relatively rapid and comprehensive degradation of albumin to small fragments (range 1-15 kDa), The degradation process is inhibited in diabetic nephropathy in proportion to the level of albuminuria detected by RIA.