Diabetic kidney disease (DKD) is among the most common and serious complications of both type 1 and type 2 diabetes. In this study, we used KK/Ta‐Ins2^Akita (KK‐Akita) mice as a model of DKD and KK/Ta (KK) mice as controls to identify novel factors related to the development/progression of DKD. Capillary electrophoresis coupled with mass spectrometry analysis revealed that circulating Asp (l‐aspartic acid) levels in diabetic KK‐Akita mice tend to be lower than those in control KK mice. Therefore, we evaluated the effect of Asp supplementation to prevent the progression of DKD in KK‐Akita mice. Mice were divided into three groups: (a) untreated KK mice (Control group), (b) untreated KK‐Akita mice (DKD group), and (c) treated (double‐volume Asp diet) KK‐Akita mice (Tx group). Kidney sections were stained with fluorescein isothiocyanate‐labeled lectins, wheat germ agglutinin (WGA), and anti‐endothelial nitric oxide synthase (eNOS) antibody for evaluation of endothelial surface layer (ESL) and NO synthesis. The mesangial area and glomerular size in the DKD group were significantly larger than those in the Control group; however, there was no significant difference in those between the DKD and Tx groups. Albuminuria, the ratio of foot process effacement, and thickness of glomerular basement membrane in the Tx group were significantly lower than those in the DKD group. Furthermore, the expression levels of glomerular WGA and microvascular eNOS in the Tx group improved significantly and approached the level in the Control group. In conclusion, the improvement of albuminuria in the Tx group may be caused by the reduction of oxidative stress in the kidneys, which may lead to the subsequent improvement of glomerular ESL.

中文翻译：

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补充天冬氨酸改善了小鼠糖尿病性肾脏疾病的症状。

糖尿病性肾脏疾病（DKD）是1型和2型糖尿病最常见和最严重的并发症之一。在这项研究中，我们使用KK / Ta- Ins 2^秋田（KK-Akita）小鼠作为DKD模型，并使用KK / Ta（KK）小鼠作为对照来识别与DKD发生/发展有关的新因素。毛细管电泳结合质谱分析显示循环中的Asp（l糖尿病KK-Akita小鼠中的天冬氨酸）水平低于对照组KK小鼠中的水平。因此，我们评估了补充Asp预防KK‐Akita小鼠DKD进展的效果。小鼠分为三组：（a）未经治疗的KK小鼠（对照组），（b）未经治疗的KK-Akita小鼠（DKD组）和（c）治疗（双倍剂量的Asp饮食）KK-Akita小鼠（Tx组） ）。肾脏切片用荧光素异硫氰酸酯标记的凝集素，小麦胚芽凝集素（WGA）和抗内皮型一氧化氮合酶（eNOS）抗体染色，以评估内皮表面层（ESL）和NO的合成。DKD组的肾小球系膜面积和肾小球大小明显大于对照组。但是，DKD和Tx组之间的差异不明显。蛋白尿 Tx组的足突消失率和肾小球基底膜厚度均明显低于DKD组。此外，Tx组中肾小球WGA和微血管eNOS的表达水平显着提高，并接近对照组。总之，Tx组蛋白尿的改善可能是由于肾脏中氧化应激的降低所致，这可能导致肾小球ESL的改善。