Effects of perspective sirtuin-1 activator on energy homeostasis constituents in rats with e xperimental t ype 2 diabetes mellitus at the background of obesity

NAD+-dependent deacetylase, sirtuin-1 (SIRT1), is a promising pharmacological target for the treatment ofage-related disorders, including obesity and type 2 diabetes mellitus (DM2). The aim of the work was to evaluate the effect of the original heterocyclic compound with the proprietary name pyrabentin with in situ provenability to activate human sirtuin-1 on the energy homeostasis components in rats with experimental DM2 andobesity. The study was conducted on adult male Wistar rats (n = 24). DM2 with obesity was induced by lowdose of streptozotocin after 100-day’s combined high-fat and high-fructose diet consumption; control sex- andage-matched animals were received standard nutrition. Pyrabentin was administered orally at 50 mg/kg bodyweight as an aqueous suspension with Tween-80 daily for 30 days. The reference drug metformin was administered in a similar way at 50 mg/kg body weight, the control group received a placebo. Glucose tolerance by theglucose oxidase method, enzyme lipid profile, abdominal adipose tissue mass by fractions, and the functionalstate of hepatocyte mitochondria by respiration intensity and oxidative phosphorylation by the polarographicmethod were evaluated. It was established that the 30-day administration of pyrabentine to rats with DM2 wasrealized in a statistically significant decrease in basal glycemia, glucose intolerance, dyslipidemia, body weightand relative weight of abdominal adipose tissue fractions with comparable efficacy to the reference drug. Thiswas accompanied by an improvement in oxidative phosphorylation and, accordingly, in the functional activity ofliver mitochondria.