Advanced glycation end products attenuate cellular insulin sensitivity by increasing the generation of intracellular reactive oxygen species in adipocytes.
Advanced glycation end products attenuate cellular insulin sensitivity by increasing the generation of intracellular reactive oxygen species in adipocytes.
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DOI：
10.1016/j.diabres.2006.09.016
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发表时间：
2007-05
影响因子：
5.1
通讯作者：
H. Unoki;H. Bujo;S. Yamagishi;M. Takeuchi;T. Imaizumi;Y. Saito
中科院分区：
文献类型：
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作者：
H. Unoki;H. Bujo;S. Yamagishi;M. Takeuchi;T. Imaizumi;Y. Saito
晚期糖基化终产物（AGE）已在各种病理条件下被观察到，特别是在糖尿病中。然而，目前尚不清楚AGE是否与脂肪组织的胰岛素抵抗有关。在本研究中，我们通过研究AGE对脂肪细胞中葡萄糖摄取和脂肪细胞分化的影响及其机制，研究了AGE对脂肪细胞胰岛素敏感性的影响。葡萄糖、甘油醛或乙醇醛衍生的AGE抑制3T3-L1细胞的分化。在没有或存在胰岛素的情况下，这些AGE也会抑制葡萄糖的摄取，这被针对AGE的抗体或AGE受体（RAGE）完全阻止。AGE增加了3T3-L1脂肪细胞内活性氧（ROS）的产生，并且通过抗氧化剂n -乙酰半胱氨酸处理完全逆转了AGE对葡萄糖摄取的影响。AGE还诱导单核细胞趋化蛋白-1的表达，该蛋白在3T3-L1脂肪细胞中与肥胖相关的葡萄糖耐受不良的发生有关。我们目前的研究表明，AGE-RAGE相互作用通过细胞内ROS的过度生成抑制葡萄糖摄取，从而表明它参与了肥胖相关胰岛素抵抗的发展。
Advanced glycation end products (AGE) have been observed in various pathological conditions especially in diabetes mellitus. However, it is unclear as to whether AGE are involved in insulin resistance in adipose tissues. In this study, we examined the effects of AGE on insulin sensitivity in adipocytes by examining the effects of AGE and its mechanisms on the glucose uptake in adipocytes and adipocyte differentiation. Glucose-, glyceraldehyde-, or glycolaldehyde-derived AGE inhibited the differentiation of 3T3-L1 cells. These AGE also inhibited the glucose uptake in the absence or presence of insulin, which were completely prevented by antibody against AGE or receptor for AGE (RAGE). The AGE increased the intracellular reactive oxygen species (ROS) generation in 3T3-L1 adipocytes, and the effects of AGE on glucose uptake were completely reversed by the treatment with an anti-oxidant, N-acetylcysteine. The AGE also induced the expression of monocyte chemoattractant protein-1, which has been implicated in the development of obesity-associated glucose intolerance, in 3T3-L1 adipocytes. Our present study suggests that AGE–RAGE interaction inhibits the glucose uptake through the overgeneration of intracellular ROS, thus indicating that it is involved in the development of obesity-related insulin resistance.