Dysfunction of human subcutaneous fat arterioles in obesity alone or obesity associated with Type 2 diabetes
Dysfunction of human subcutaneous fat arterioles in obesity alone or obesity associated with Type 2 diabetes
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DOI：
10.1042/cs20100355
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发表时间：
2011-05-01
期刊：
影响因子：
6
通讯作者：
Tudor, Aura
中科院分区：
文献类型：
--
作者：
Georgescu, Adriana;Popov, Doina;Tudor, Aura
本研究的目的是研究肥胖单独和肥胖与2型糖尿病的结构，血管反应性和对胰岛素的反应，分离的人皮下脂肪小动脉的影响，这些影响与胰岛素信号蛋白的表达。在手术过程中剥离脐周皮下脂肪组织，解剖出小动脉（内径220 +/- 40 μ m），并通过电子显微镜、肌造影和免疫印迹进行研究。与瘦人相比，肥胖激活了皮下小动脉内皮细胞，增加了血管壁胶原的积聚，增加了肾上腺素能反应的敏感性;肥胖也减少了eNOS（内皮NO合酶）蛋白表达、NO产生以及内皮依赖性和胰岛素诱导的血管舒张，以及IRS（胰岛素受体底物）-1和IRS-2以及胰岛素信号传导途径中的下游分子如PI 3 K（磷酸肌醇3-激酶）、磷酸-Akt和Akt的蛋白质表达。当肥胖与2型糖尿病相关时，这些变化显着增强。总之，肥胖单独或肥胖与2型糖尿病改变人类脐周脂肪组织小动脉的结构，功能和生化，包括eNOS表达减少和IRS-1，IRS-2，PI 3 K和Akt的胰岛素信号通路的水平降低。
The aim of the present study was to examine the effects of obesity alone and obesity associated with Type 2 diabetes on the structure, vascular reactivity and response to insulin of isolated human subcutaneous fat arterioles; these effects were correlated with the expression of insulin signalling proteins. Periumbilical subcutaneous adipose tissue was explanted during surgery, small arterioles (internal diameter 220 +/- 40 mu m) were dissected out and investigated by electron microscopy, myography and immunoblotting. Compared with the subcutaneous arterioles of lean subjects, obesity activated the endothelium, enhanced the accumulation of collagen within vascular wall and increased the sensitivity of adrenergic response; obesity also diminished eNOS (endothelial NO synthase) protein expression, NO production, and endothelium-dependent and insulin-induced vasodilatation, as well as the protein expression of both IRS (insulin receptor substrates)-1 and IRS-2 and of the downstream molecules in the insulin signalling pathway, such as PI3K (phosphoinositide 3-kinase), phospho-Akt and Akt. When obesity was associated with Type 2 diabetes, these changes were significantly augmented. In conclusion, obesity alone or obesity associated with Type 2 diabetes alters human periumbilical adipose tissue arterioles in terms of structure, function and biochemsitry, including diminished eNOS expression and reduced levels of IRS-1, IRS-2, PI3K and Akt in the insulin signalling pathway.