首页> 外文期刊>American Journal of Physiology >Endothelial dysfunction in Type 2 diabetes correlates with deregulated expression of the tail-anchored membrane protein SLMAP.
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Endothelial dysfunction in Type 2 diabetes correlates with deregulated expression of the tail-anchored membrane protein SLMAP.

机译:2型糖尿病的内皮功能障碍与尾锚膜蛋白SLMAP的表达失调有关。

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The Type 2 diabetic db/db mouse experiences vascular dysfunction typified by changes in the contraction and relaxation profiles of small mesenteric arteries (SMAs). Contractions of SMAs from the db/db mouse to the alpha1-adrenoceptor agonist phenylephrine (PE) were significantly enhanced, and acetylcholine (ACh)-induced relaxations were significantly depressed. Drug treatment of db/db mice with a nonthiazolidinedione peroxisome prolifetor-activated receptor-gamma agonist and insulin sensitizing agent 2-[2-(4-phenoxy-2-propylphenoxy)ethyl]indole-5-acetic acid (COOH) completely prevented the changes in endothelium-dependent relaxation, but, with the discontinuation of therapy, endothelial dysfunction returned. Dysfunctional SMAs were found to specifically upregulate the expression of a 35-kDa isoform of sarcolemmal membrane-associated protein (SLMAP), which is a component of the excitation-contraction coupling apparatus and implicated in the regulation of membrane function in muscle cells. Real-time PCR revealed high SLMAP mRNA levels in the db/db microvasculature, which were markedly downregulated during COOH treatment but elevated again when drug therapy was discontinued. These data reveal that the microvasculature in db/db mice undergoes significant changes in vascular function with the endothelial component of vascular dysfunction specifically correlating with the overexpression of SLMAP. Thus changes in SLMAP expression may be an important indicator for microvascular disease associated with Type 2 diabetes.
机译:2型糖尿病db / db小鼠经历血管功能障碍,典型表现为小肠系膜动脉(SMA)的收缩和舒张曲线变化。从db / db小鼠到α1-肾上腺素受体激动剂去氧肾上腺素(PE)的SMA收缩显着增强,而乙酰胆碱(ACh)诱导的舒张则显着降低。用非噻唑烷二酮过氧化物酶体增殖物激活的受体-γ激动剂和胰岛素敏化剂2- [2-(4-苯氧基-2-丙基苯氧基)乙基]吲哚-5-乙酸(COOH)对db / db小鼠进行药物治疗。内皮依赖性舒张功能的改变,但随着治疗的停止,内皮功能障碍又恢复了。发现功能失调的SMAs特异性上调了肌膜结合蛋白(SLMAP)的35kDa同种型的表达,该蛋白是刺激-收缩偶联设备的一个组成部分,与肌肉细胞膜功能的调节有关。实时PCR显示db / db微脉管系统中SLMAP mRNA水平较高,在COOH治疗期间明显下调,但在停止药物治疗时再次升高。这些数据表明,db / db小鼠的微脉管系统的血管功能发生了显着变化,其中血管功能障碍的内皮成分与SLMAP的过度表达特别相关。因此,SLMAP表达的变化可能是与2型糖尿病相关的微血管疾病的重要指标。

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