Department of Translational Medicine, Federico II University of Naples, Italy.
Department of Advanced Biomedical Sciences, Federico II University of Naples, Italy.
Monaldi Arch Chest Dis. 2021 Mar 11;91(2). doi: 10.4081/monaldi.2021.1602.
Insulin resistance (IR) and the related hyperinsulinamia play a key role in the genesis and progression of the continuum of cardiovascular (CV) disease. Thus, it is reasonable to pursue in primary and secondary CV prevention, the pharmacological strategies that are capable to interfere with the development of IR. The renin-angiotensin-aldosterone system (RAAS) plays an important role in the pathogenesis of IR. In particular, angiotensin II (Ang II) through the generation of reactive oxygen species, induces a low grade of inflammation, which impairs the insulin signal transduction. The angiotensin converting enzyme (ACE) inhibitors are effective not only as blood pressure-lowering agents, but also as modulators of metabolic abnormalities. Indeed, experimental evidence indicates that in animal models of IR, ACE inhibitors are capable to ameliorate the insulin sensitivity. The Ang II receptor blockers (ARBs) modulate the peroxisome proliferator-activated receptor (PPAR)-γ activity. PPARâ€"γ is a transcription factor that controls the gene expression of several key enzymes of glucose metabolism. A further mechanism that accounts for the favorable metabolic properties of ARBs is the capability to modulate the hypothalamicâ€"pituitary-adrenal (HPA) axis. The available clinical evidence is consistent with the concept that both ACE inhibitors and ARBs are able to interfere with the development of IR and its consequences like type 2 diabetes. In addition, pharmacological inhibition of the RAAS has favourable effects on dyslipidaemias, metabolic syndrome and obesity. Therefore, the pharmacological antagonism of the RAAS, nowadays, represents the first choice in the prevention of cardio-metabolic diseases.
胰岛素抵抗（IR）和相关的高胰岛素血症在心血管（CV）疾病连续体的发生和进展中起着关键作用。因此，在一级和二级 CV 预防中，追求能够干扰 IR 发展的药理学策略是合理的。肾素-血管紧张素-醛固酮系统（RAAS）在 IR 的发病机制中起着重要作用。特别是血管紧张素 II（Ang II）通过产生活性氧，引起低度炎症，从而损害胰岛素信号转导。血管紧张素转换酶（ACE）抑制剂不仅作为降压药有效，而且作为代谢异常的调节剂。事实上，实验证据表明，在 IR 的动物模型中，ACE 抑制剂能够改善胰岛素敏感性。血管紧张素 II 受体阻滞剂（ARB）调节过氧化物酶体增殖物激活受体（PPAR）-γ活性。PPAR-γ是一种转录因子，控制着葡萄糖代谢的几个关键酶的基因表达。ARB 具有有利代谢特性的另一个机制是调节下丘脑-垂体-肾上腺（HPA）轴的能力。现有的临床证据与 ACE 抑制剂和 ARB 均能够干扰 IR 及其后果（如 2 型糖尿病）的发展的概念是一致的。此外，RAAS 的药理学抑制对血脂异常、代谢综合征和肥胖有有利影响。因此，RAAS 的药理学拮抗作用，如今，代表了预防心脏代谢疾病的首选方法。
