目的:沙库必曲-缬沙坦,最近批准的心力衰竭治疗方法,已显示出作为糖尿病可能的治疗选择的一些希望。尚不清楚这些有益作用是否与缬沙坦作用相当。在这项工作中,我们旨在研究在高脂高果糖饮食诱导的糖尿病模型中,沙库必曲-缬沙坦对代谢变化的影响,与仅由缬沙坦引起的代谢变化相比。
方法:大鼠随意喂食标准食物加自来水饮用(对照)或60%牛脂和10%果糖饮用水(患病),持续11周。从第9周开始,每组被细分为四个,即车辆,吡格列酮,Sacubitril-缬沙坦和缬沙坦。在第9至11周施用治疗,同时将大鼠维持在其各自的饮食组中。
结果:沙库必曲-缬沙坦治疗显著降低了每日食物摄入量,体重和附睾白色脂肪重量,和正常的胰岛素和糖化血红蛋白在高脂肪高果糖。缬沙坦和沙库比曲-缬沙坦都只能减轻空腹血糖水平的升高,葡萄糖,患病大鼠的胰岛素和丙酮酸耐受性以及蛋白激酶B磷酸化增加。
结论:沙巴曲缬沙坦可能是糖尿病相关代谢异常的有效调节剂,优于仅缬沙坦。
OBJECTIVE: Sacubitril-valsartan, a recently approved treatment for heart failure, has shown some promise as a possible therapeutic option for diabetes mellitus. It is still not clear whether those beneficial effects are comparable to valsartan effects. In this work, we aimed at investigating Sacubitril-valsartan effect on metabolic changes in a model of high-fat high fructose diet-induced diabetes mellitus, in comparison to the metabolic changes induced by valsartan only.
METHODS: Rats were ad libitum fed with either standard chow plus tap water for drinking (controls) or 60% beef tallow and 10% fructose drinking water (diseased) for 11 weeks. Starting in week 9, each group was subdivided into four, namely vehicle, pioglitazone, Sacubitril-valsartan and valsartan. Treatments were administered from weeks 9 to 11, while rats were maintained in their respective diet groups.
RESULTS: Sacubitril-valsartan treatment significantly decreased daily food intake, body weight and epididymal white adipose weight, and normalized insulin and glycosylated haemoglobin in high-fat high fructose. Both valsartan and Sacubitril-valsartan only attenuated the elevated fasting blood glucose levels, glucose, insulin and pyruvate tolerance and increased protein kinase B phosphorylation in diseased rats.
CONCLUSIONS: Sacubitril-valsartan may be an effective modulator of diabetes mellitus-associated metabolic aberration, superiorly compared to valsartan only.