Department of Cardiology, Beijing Friendship Hospital, Capital Medical University, 95 Yong An Road, West district, Beijing 100050, China.
Department of Cardiology, Beijing Friendship Hospital, Capital Medical University, 95 Yong An Road, West district, Beijing 100050, China.
Biomed Pharmacother. 2017 Nov;95:129-136. doi: 10.1016/j.biopha.2017.08.041. Epub 2017 Sep 12.
The effects of telmisartan on insulin-resistant properties and expression of adiponectin receptors (AdipoRs) were investigated. A diabetic rat model was established using a high-fat diet and streptozotocin (25mg/kg) and primary rat coronary vascular smooth muscle cells (VSMCs) were used to elucidate the underlying mechanisms. The diabetic rats were insulin-resistant and exhibited weight gain, elevated blood pressures, and increased plasma triglyceride levels. These manifestations were ameliorated by elmisartan treatment. Four-week telmisartan therapy increased plasma adiponectin and decreased TNF-α expression in the coronary artery. Moreover, telmisartan significantly decreased AdipoR1 and AdipoR2 expression. Using high glucose-treated rat coronary VSMCs, telmisartan and PPAR-γ agonist GW1929 prominently stimulated PPAR-γ and decreased TNF-α expression. Interestingly, telmisartan or GW1929 also prevented hyperglycemia-induced downregulation of AdipoR1 and AdipoR2 expression. Additionally, GW9662 (PPAR-γ antagonist) significantly decreased the effects of telmisartan on AdipoR1 and AdipoR2 expression. These results demonstrated that telmisartan effectively ameliorated coronary insulin resistance and inflammation in diabetic rats and upregulated AdipoR1/R2 expression via activation of PPAR-γ in the coronary artery and VSMCs.
本研究旨在探讨替米沙坦对胰岛素抵抗特性及脂联素受体（AdipoRs）表达的影响。采用高脂饮食联合链脲佐菌素（25mg/kg）建立糖尿病大鼠模型，并使用原代大鼠冠状动脉血管平滑肌细胞（VSMCs）来阐明其潜在机制。糖尿病大鼠表现出胰岛素抵抗，体重增加，血压升高，血浆甘油三酯水平升高，而替米沙坦治疗可改善这些表现。替米沙坦治疗 4 周可增加血浆脂联素水平，并降低冠状动脉中 TNF-α的表达。此外，替米沙坦可显著降低 AdipoR1 和 AdipoR2 的表达。用高糖处理的大鼠冠状动脉 VSMCs 发现，替米沙坦和 PPAR-γ 激动剂 GW1929 可明显刺激 PPAR-γ，降低 TNF-α的表达。有趣的是，替米沙坦或 GW1929 还可防止高血糖诱导的 AdipoR1 和 AdipoR2 表达下调。此外，GW9662（PPAR-γ 拮抗剂）可显著降低替米沙坦对 AdipoR1 和 AdipoR2 表达的影响。这些结果表明，替米沙坦可有效改善糖尿病大鼠的冠状动脉胰岛素抵抗和炎症，并通过在冠状动脉和 VSMCs 中激活 PPAR-γ来上调 AdipoR1/R2 的表达。
