%0 Journal Article
%T The dual inhibitor Sacubitril-valsartan ameliorate high-fat high-fructose-induced metabolic disorders in rats superiorly compared to valsartan only.
%A Abo-Khookh AM
%A Ghoneim HA
%A Abdelaziz RR
%A Nader MA
%A Shawky NM
%J J Pharm Pharmacol
%V 75
%N 6
%D Jun 2023 5
%M 36966365
%F 4.81
%R 10.1093/jpp/rgad012
%X <B>OBJECTIVE: </B>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.<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>Sacubitril-valsartan may be an effective modulator of diabetes mellitus-associated metabolic aberration, superiorly compared to valsartan only.