Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
J Pharm Pharmacol. 2023 Jun 5;75(6):846-858. doi: 10.1093/jpp/rgad012.
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.
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.
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.
Sacubitril-valsartan may be an effective modulator of diabetes mellitus-associated metabolic aberration, superiorly compared to valsartan only.
沙库巴曲缬沙坦是一种最近被批准用于心力衰竭的治疗药物，它在治疗糖尿病方面显示出了一定的前景，可能成为一种治疗选择。目前尚不清楚这些有益的效果是否与缬沙坦的效果相当。在这项工作中，我们旨在研究沙库巴曲缬沙坦对高脂肪高果糖饮食诱导的糖尿病模型代谢变化的影响，与仅缬沙坦引起的代谢变化进行比较。
大鼠自由饮用标准饲料加自来水（对照组）或 60%牛脂加 10%果糖水（患病组），共 11 周。从第 9 周开始，每组再分为四组，即载体组、吡格列酮组、沙库巴曲缬沙坦组和缬沙坦组。从第 9 周到第 11 周给予治疗，同时大鼠保持在各自的饮食组中。
沙库巴曲缬沙坦治疗可显著降低高脂肪高果糖饮食大鼠的日摄食量、体重和附睾白色脂肪重量，并使胰岛素和糖化血红蛋白正常化。缬沙坦和沙库巴曲缬沙坦均可减轻患病大鼠的空腹血糖水平升高、葡萄糖、胰岛素和丙酮酸耐量以及蛋白激酶 B 磷酸化的增加。
与仅用缬沙坦相比，沙库巴曲缬沙坦可能是一种治疗糖尿病相关代谢异常的有效调节剂。
