de Carvalho Maria Helena C, Colaço André Luiz, Fortes Zuleica Bruno
Laboratório de Hipertensão e Diabetes, Departamento de Farmacologia, Instituto de Ciências Biomédicas, Universidade de São PauloSão Paulo, SP.
Arq Bras Endocrinol Metabol. 2006 Apr;50(2):304-12. doi: 10.1590/s0004-27302006000200016. Epub 2006 May 23.
Endothelial dysfunction is associated with several vascular conditions as atherosclerosis, hypertension, hyperlipidemia and diabetes mellitus. In all these conditions insulin resistance (IR) is present. Cytokines are low molecular weight proteins with several endocrine and metabolic functions that participate of inflammation and immune response. Several of these cytokines are independent risk factors for cerebrovascular and coronary artery disease. The major sources of cytokines (adipokines) are the visceral and subcutaneous adipose tissues. Thus, increased adipose tissue mass is associated with alteration in adipokine production as over expression of tumor necrosis factor alpha, interleukin 6, plasminogen activator inhibitor 1, and under expression of adiponectin in adipocite tissue. The pro-inflammatory status associated with these changes provides a potential link between IR and endothelial dysfunction, the early stage in the atherosclerotic process, in obese individuals, and type 2 diabetic patients. Reduction of adipose tissue mass through weight reduction in association with exercise reduces TNF-alpha, IL-6, and PAI-1, increases adiponectin, and is associated with improved insulin sensitivity and endothelial function. This review will focus on the evidence for regulation of endothelial function by insulin and the adypokines such as adyponectin, leptin, resistin, IL-6 and TNF-alpha. Interaction between insulin signaling and adypokines will be discussed, as well as the concept that aberrant adypokine secretion in IR and/or obesity impairs endothelial function and contributes further to reduce insulin sensitivity.
内皮功能障碍与多种血管疾病相关，如动脉粥样硬化、高血压、高脂血症和糖尿病。在所有这些疾病中都存在胰岛素抵抗（IR）。细胞因子是具有多种内分泌和代谢功能的低分子量蛋白质，参与炎症和免疫反应。其中几种细胞因子是脑血管和冠状动脉疾病的独立危险因素。细胞因子（脂肪因子）的主要来源是内脏和皮下脂肪组织。因此，脂肪组织量增加与脂肪因子产生的改变有关，如脂肪细胞组织中肿瘤坏死因子α、白细胞介素6、纤溶酶原激活物抑制剂1的过度表达以及脂联素的表达不足。与这些变化相关的促炎状态为肥胖个体和2型糖尿病患者中IR与内皮功能障碍（动脉粥样硬化过程的早期阶段）之间提供了潜在联系。通过减重并结合运动减少脂肪组织量可降低肿瘤坏死因子α、白细胞介素6和纤溶酶原激活物抑制剂1，增加脂联素，并与胰岛素敏感性和内皮功能改善相关。本综述将聚焦于胰岛素和脂联素、瘦素、抵抗素、白细胞介素6和肿瘤坏死因子α等脂肪因子对内皮功能调节的证据。将讨论胰岛素信号与脂肪因子之间的相互作用，以及IR和/或肥胖中异常脂肪因子分泌损害内皮功能并进一步导致胰岛素敏感性降低的概念。
