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内皮功能障碍可导致兼具胰岛素抵抗特征的心血管疾病。胰岛素抵抗是2型糖尿病、肥胖以及代谢综合征等一系列代谢紊乱的标志,而这些代谢紊乱具有内皮功能障碍的特征。促进葡萄糖处理的胰岛素代谢反应可被内皮中胰岛素的血管反应增强以刺激血管扩张剂NO的产生。事实上,由胰岛素刺激所产生的葡萄糖摄取量的增加中,25%~40%可通过骨骼肌中NO-依赖性血流的增加来解释。与NO产生相关的内皮中3-磷酸激酶依赖的胰岛素信号通路,与骨骼肌中促进葡萄糖摄取的代谢通路有着惊人的相似。其他已经明确的非代谢性旁路调节内皮中血管收缩药内皮因子-1(ET-1)的分泌。代谢性胰岛素抵抗具有在3-磷酸激酶依赖信号通路特异性损坏的特征,在内皮中,这也许会引起NO产生和ET-1分泌的失衡,从而导致血流减少继而使胰岛素抵抗加剧。在动物和人类中开展的治疗性干预证明,改善内皮功能可改善胰岛素抵抗,同时改善胰岛素敏感性可改善内皮功能障碍。总之,细胞学、生理学、临床医学以及流行病学研究都强烈支持内皮功能障碍与胰岛素抵抗存在相互关系,这种关系有助于将心血管疾病和代谢疾病联系起来。本综述将讨论内皮功能障碍和胰岛素抵抗的相关病理生理学机制,并重点强调这个机制对代谢综合症的治疗意义。
Endothelial dysfunction can lead to cardiovascular disease characterized by insulin resistance. Insulin resistance is a hallmark of a series of metabolic disorders such as type 2 diabetes, obesity and metabolic syndrome, which are characterized by endothelial dysfunction. Insulin metabolic responses that promote glucose treatment can be enhanced by the vascular response of insulin in the endothelium to stimulate the production of vasodilator NO. In fact, 25% to 40% of the increase in glucose uptake produced by insulin stimulation can be explained by an increase in NO-dependent blood flow in skeletal muscle. Endothelial 3-phosphate kinase-dependent insulin signaling pathways associated with NO production have striking similarities with the metabolic pathways that promote glucose uptake in skeletal muscle. Other well-established non-metabolic bypass regulates the secretion of endothelium, vasoconstrictor drug endothelin-1 (ET-1). Metabolic insulin resistance is characterized by specific damage in the 3-phosphokinase-dependent signaling pathway, which in the endothelium may cause an imbalance between NO production and ET-1 secretion, resulting in decreased blood flow which in turn exacerbates insulin resistance. Therapeutic interventions in animals and humans demonstrate that improving endothelial function improves insulin resistance and improving insulin sensitivity improves endothelial dysfunction. In summary, cytology, physiology, clinical medicine and epidemiological studies all strongly support the existence of a relationship between endothelial dysfunction and insulin resistance, a relationship that helps to link cardiovascular and metabolic diseases. This review will discuss the pathophysiological mechanisms underlying endothelial dysfunction and insulin resistance with emphasis on the therapeutic implications of this mechanism for metabolic syndrome.