insulin resistance, obesity, sirtuin-1 activator, metabolic memory, rats


Pharmacological activation of sirtuin-1 (SIRT1), which can mimic calorie restriction, reduce fat deposition along with stimulating its utilization, and possibly erase "metabolic memory", is a promising goal for the prevention and treatment of obesity and type 2 diabetes. The aim of the study was to evaluate the specific antidiabetic effect of the original heterocyclic compound with the proprietary name pyrabentin with in situ proven ability to activate human sirtuin-1 on the experimental model of "metabolic memory" in rats.

The study was conducted on adult male Wistar rats (n=24), which were kept on a high-fat diet (HFD) for 5 months, control sex- and age-matched animals (n=6) were received standard diet (StD). At the end of the 5-mo HFD-period, the animals were randomized for the study over the next two months into 4 groups as follows: HFD/HFD+placebo, HFD/StD+placebo, HFD/StD+pyrabentin (PB), HFD/StD+metformin (MF). PB was administered orally at 50 mg/kg body weight as an aqueous suspension with Tween-80 daily, the reference drug metformin was administered in a similar way at 100 mg/kg body weight, the control group received a placebo. Glucose tolerance test and short insulin test were performed, body weight, abdominal adipose tissue weight by fraction and blood pressure were assessed. Shapiro-Wilk test, paired and unpaired Student’s t-test, and Mann-Whitney U-test were used.

It was found that 60-day administration of pyrabentin to rats with a model of "metabolic memory", insulin resistance and obesity, was realized in a statistically significant decrease in basal glycemia, glucose intolerance, body weight and weight of abdominal adipose tissue fractions with comparable efficacy to the reference drug. This was accompanied by improved insulin sensitivity and blood pressure.


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How to Cite

Krasova, N., Gladkih, A., Yaremenko, F., Leshchenko, Z., Kolesnikova, A., Gromakovska, O., Lipson, V., & Poltorak, V. (2021). STUDY OF SPECIFIC ANTIDIABETIC EFFECT OF PERSPECTIVE SIRTUIN-1 ACTIVATOR PYRABENTIN ON THE MODEL OF METABOLIC MEMORY IN RATS. Problems of Endocrine Pathology, 76(2), 71-77.

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