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
Keywords:experimental type 2 diabetes mellitus, obesity, sirtuin-1 activator, energy homeostasis
NAD+-dependent deacetylase, sirtuin-1 (SIRT1), is a promising pharmacological target for the treatment of
age-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 proven
ability to activate human sirtuin-1 on the energy homeostasis components in rats with experimental DM2 and
obesity. The study was conducted on adult male Wistar rats (n = 24). DM2 with obesity was induced by low
dose of streptozotocin after 100-day’s combined high-fat and high-fructose diet consumption; control sex- and
age-matched animals were received standard nutrition. Pyrabentin was administered orally at 50 mg/kg body
weight 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 the
glucose oxidase method, enzyme lipid profile, abdominal adipose tissue mass by fractions, and the functional
state of hepatocyte mitochondria by respiration intensity and oxidative phosphorylation by the polarographic
method were evaluated. It was established that the 30-day administration of pyrabentine to rats with DM2 was
realized in a statistically significant decrease in basal glycemia, glucose intolerance, dyslipidemia, body weight
and relative weight of abdominal adipose tissue fractions with comparable efficacy to the reference drug. This
was accompanied by an improvement in oxidative phosphorylation and, accordingly, in the functional activity of
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