Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
J Hypertens. 2009 Dec;27(12):2409-20. doi: 10.1097/HJH.0b013e3283310e1b.
Angiotensin II (Ang II) has been shown to contribute to the pathogenesis of hypertension and insulin resistance. In addition, administration of selective Ang II type-1 receptor blockers has been shown to improve insulin sensitivity. However, only a few studies have addressed the molecular mechanisms involved in this association.
The current study was undertaken to determine whether an Ang II receptor blocker (irbesartan) is effective in improving insulin resistance in adipose tissue from obese Zucker rats, a model of metabolic syndrome.
Ten-week-old male obese Zucker rats (fa/fa) were treated daily with either vehicle or 50 mg/kg irbesartan for 6 months, and their age-matched lean (+/?) (lean Zucker rats) was used as a control. We determined systolic blood pressure (SBP), together with plasma levels of insulin, triglycerides, cholesterol and glucose. In addition, we evaluated insulin signaling through the insulin receptor/insulin receptor substrate-1/phosphatidylinositol 3 kinase/Akt/glucose transporter 4 pathway as well as the inflammatory status of adipose tissue.
Obese Zucker rats displayed hyperglycemia, hypertriglyceridemia, hyperinsulinemia and hypercholesterolemia and increased SBP together with decreased activation of insulin signaling through the insulin receptor/insulin receptor substrate-1/phosphatidylinositol 3 kinase/Akt pathway in adipose tissue as well as increased adipocytes size, macrophage infiltration and augmented levels of inflammatory mediators such tumor necrosis factor-alpha, monocyte chemoattractant protein-1 and Ang II. Chronic irbesartan treatment resulted in an improvement of all alterations.
The present study provides substantial information that demonstrates that long-term selective Ang II blockade ameliorates insulin resistance in adipose tissue from a model of metabolic syndrome via a mechanism that could involve the modulation of insulin signaling.
血管紧张素 II（Ang II）已被证明有助于高血压和胰岛素抵抗的发病机制。此外，给予选择性血管紧张素 II 型 1 受体阻滞剂已被证明可改善胰岛素敏感性。然而，只有少数研究涉及与此关联相关的分子机制。
本研究旨在确定血管紧张素 II 受体阻滞剂（厄贝沙坦）是否能有效改善肥胖 Zucker 大鼠（代谢综合征模型）脂肪组织的胰岛素抵抗。
10 周龄雄性肥胖 Zucker 大鼠（fa/fa）每日用载体或 50mg/kg 厄贝沙坦治疗 6 个月，并用年龄匹配的 lean（+/?）（瘦 Zucker 大鼠）作为对照。我们测定了收缩压（SBP），以及血浆胰岛素、甘油三酯、胆固醇和葡萄糖水平。此外，我们评估了胰岛素受体/胰岛素受体底物-1/磷酸肌醇 3 激酶/Akt/葡萄糖转运蛋白 4 通路的胰岛素信号转导以及脂肪组织的炎症状态。
肥胖 Zucker 大鼠表现出高血糖、高甘油三酯血症、高胰岛素血症和高胆固醇血症，以及 SBP 升高，同时脂肪组织中胰岛素受体/胰岛素受体底物-1/磷酸肌醇 3 激酶/Akt 通路的胰岛素信号转导降低，脂肪细胞增大，巨噬细胞浸润增加，炎症介质如肿瘤坏死因子-α、单核细胞趋化蛋白-1 和 Ang II 水平升高。慢性厄贝沙坦治疗可改善所有这些改变。
本研究提供了大量信息，表明长期选择性血管紧张素 II 阻断可通过调节胰岛素信号转导改善代谢综合征模型脂肪组织的胰岛素抵抗。
