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    標題: Telmisartan is effective to ameliorate metabolic syndrome in rat model - a preclinical report
    作者: Chen, Kai-Chun
    Li, Yingxiao
    Chang, Wei-Ting
    Kuo, Feng Yu
    Chen, Zhih-Cherng
    Cheng, Juei-Tang
    貢獻者: Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Psychosomat Internal Med
    Chi Mei Med Ctr, Dept Med Res
    Chi Mei Med Ctr, Dept Cardiol
    Kaohsiung Vet Gen Hosp, Cardiovasc Ctr
    Chia Nan Univ Pharm & Sci, Dept Pharm
    Chang Jung Christian Univ
    關鍵字: metabolic syndrome
    telmisartan
    PPAR delta
    GSK0660
    diet
    日期: 2018
    上傳時間: 2019-11-15 15:43:59 (UTC+8)
    出版者: DOVE MEDICAL PRESS LTD
    摘要: Background: Metabolic syndrome (MS) is known to be associated with hypertension, insulin resistance, and dyslipidemia, and it raises the risk for cardiovascular diseases and diabetes mellitus. Telmisartan is used in clinic as an angiotensin II receptor blocker and it is also identified as activating peroxisome proliferator-activated receptors delta (PPAR delta). Activation of PPAR delta produced beneficial effects on fatty acid metabolism and glucose metabolism. This study aims to investigate the effects of telmisartan on the modulation of MS in rats fed a high-fat/high-sodium diet. Methods: Rats were fed with a high-fat/high-sodium diet and received injections of streptozotocin at low dose to induce MS. Then, rats with MS were treated with telmisartan. The weight, glucose tolerance, and insulin sensitivity were measured. The lipid profiles were also obtained. The weights of retroperitoneal and epididymal fat pads were determined. The role of PPR delta in telmisartan treatment was identified in rats pretreated with the specific antagonist GSK0660. Results: The results showed that telmisartan, but not losartan, significantly reduced plasma glucose and plasma insulin, and improved insulin resistance in rats with MS. Telmisartan also decreased blood pressure and lipids more significantly than losartan. Moreover, GSK0660 effectively reversed the effects of telmisartan in the MS rats. In the MS group, telmisartan activated PPAR delta to enhance the levels of phosphorylated GLUT4 in muscle or the expression of phosphoenolpyruvate carboxykinase (PIRPCK) in the liver, which was also abolished by GSK0660. Telmisartan is useful to ameliorate hypertension and insulin resistance in rats with MS. Telmisartan improves the insulin resistance through increased expression of GLUT4 and down-regulation of PEPCK via PPAR delta-dependent mechanisms. Conclusion: Telmisartan has been proven to ameliorate MS, particularly in the prediabetes state. Therefore, telmisartan is suitable to develop for the management of MS in clinics.
    link: http://dx.doi.org/10.2147/DMSO.S187092
    關聯: International Journal of Chronic Obstructive Pulmonary Disease, v.11, pp.901-911
    Appears in Collections:[藥學系(所)] 期刊論文

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