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正常生理状态下,胰岛素不仅通过磷脂酰肌醇3-激酶(PI3K)途径产生血管舒张以及促生存作用,还通过有丝分裂原活化蛋白激酶(MAPK)途径在血管培养基上产生血管收缩及致有丝分裂作用。而在胰岛素抵抗状态下,通过PI3K途径转导的胰岛素信号变迟缓,但是通过MARK级联反应途径的信号仍然如常。这种不平衡使胰岛素抵抗者有更多的患高血压及动脉粥样硬化的倾向。肾素血管紧张素系统(RAS)在心血管系统的全身及局部都有表达。胰岛素抵抗上调局部RAS反应,这对高血压、心衰及动脉粥样硬化都有作用。血管紧张素II损伤胰岛素信号转导途径,通过NF-κB途径产生炎症,减少一氧化氮的利用及促进血管收缩,从而导致胰岛素抵抗和血管内皮功能障碍。因此,RAS,胰岛素抵抗和炎症的共存协同导致内皮功能紊乱、血管损伤及动脉粥样硬化。RAS的抑制使心血管和肾脏疾病的发病率及死亡率及新发的2型糖尿病的发病率下降。
Under normal physiological conditions, insulin not only produces vasodilatory and pro-survival effects via the phosphatidylinositol 3-kinase (PI3K) pathway, but also produces vasoconstriction and mitogenic effects on vascular media by the mitogen-activated protein kinase (MAPK) pathway . In the insulin resistance state, however, the insulin signal transduced by the PI3K pathway becomes retarded, but the signal through the MARK cascade remains the same. This imbalance gives insulin resistance more susceptibility to hypertension and atherosclerosis. The renin-angiotensin system (RAS) is expressed both systemically and locally in the cardiovascular system. Insulin resistance upregulates the local RAS response, which has effects on hypertension, heart failure and atherosclerosis. Angiotensin II impairs the insulin signaling pathway, producing inflammation through the NF-κB pathway, reducing nitric oxide utilization and promoting vasoconstriction, leading to insulin resistance and endothelial dysfunction. Therefore, coexistence of RAS, insulin resistance and inflammation leads to endothelial dysfunction, vascular damage and atherosclerosis. Inhibition of RAS decreases the incidence and mortality of cardiovascular and renal diseases and the incidence of newly diagnosed type 2 diabetes.