STUDY OF SPECIFIC ANTIDIABETIC EFFECT OF PERSPECTIVE SIRTUIN-1 ACTIVATOR PYRABENTIN ON THE MODEL OF METABOLIC MEMORY IN RATS

Authors

DOI:

https://doi.org/10.21856/j-PEP.2021.2.10

Keywords:

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

Abstract

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.

References

International Diabetes Federation. Diabetes Atlas. – 9th Еd. – Brussels, 2019. – 176 р.

Voss, T. C. Dinamic regulation of transcriptional states by chromatin and transcription factors [Text] / T. C. Voss, G. L. Hager // Nat. Rev. Genet. – 2014. - Vol. 15. - P. 69-81.

Sirtuins: molecular traffic lights in the crossroad of oxidative stress, chromatin remodeling, and transcription [Text] / R. Ramkumar, G. Richa, K. D. Marija, D. Constantinos // J. Biomed. Biotechnol. – 2011. – Vol. 2011. – P. 1-17.

Sirtuins and their biological relevance in aging and age-related diseases [Text] / L. Zhao, J. Cao, K. Hu [et al.] // Aging and Disease. – 2020. – Vol. 11, № 4. – P. 927-945.

Пат. 121946 UA, МПК А61К 31/54(2006.01), А61Р 3/10(2006.01), C07D 231/10(2006.01), C07D 243/12(2006.01), C07D 279/04(2006.01). 5-[2-(1,3-Диметил-1H-піразол-4-іл)-2,3-дигідро-1H-1,5-бензодіазепін-4-іл]-4-гідрокси-2H-1,3-тіазин-2,6(3H)-діон, що виявляє комплексну антидіабетичну активність на тлі ожиріння, та спосіб його одержання (варіанти) [Текст] / Ю. І. Караченцев, С. О. Зозуля, Ф. Г. Яременко [та ін.] (UA) ; заявник ДУ "Інститут проблем ендокринної патології ім. В. Я. Данилевського НАМН України", Київський національний університет імені Тараса Шевченка (UA). – № a 2019 05275 ; заявл. 17.05.2019 ; опубл. 10.09.19, Бюл. № 17. – 15 с.

Metformin improves metabolic memory in high fat diet (HFD)-induced renal dysfunction [Text] / K. Tikoo, E. Sharma, V. Rao Amara [et al.] // J. Biol. Chem. – 2016. – Vol. 291, № 42. – Р. 21848–21856.

Лабораторные животные [Текст] / И. П. Западнюк, В. И. Западнюк, Е. А. Захария [и др.]. – К. : Вища школа, 1983. – 383 с.

Полторак, В. В. Методичні рекомендації з експериментального вивчення нових гіпоглікемічних засобів [Текст] / В. В. Полторак, Н. І. Горбенко // Доклінічні дослідження лікарських засобів / за ред. О. В. Стефанова. – К., 2001. – С. 396-408.

The short insulin tolerance test for determination of insulin sensitivity: a comparison with euglycaemic clamp [Теxt] / A. Akinmokun, P. Selby, K. Ramaiya [et al.] // Diabet. Med. – 1992. – Vol. 9, № 5. – P. 432-437.

Загальні етичні принципи експериментів на тваринах [Текст] // Ендокринологія. – 2003. – Т. 8, № 1. – С. 142-145.

Royston, J. An extension of Shapiro and Wilk’s W test for normality to large samples [Теxt] / J. P. Royston // Applied Statistic. – 1992. – Vol. 31. – Р. 115-124.

Атраментова, Л. Статистичні методи в біології [Текст] : підручник / Л. Атраментова, О. Утєвська. – Х. : ХНУ ім. В. Н. Каразіна, 2007. – 288 с.

Downloads

Published

2021-06-10

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. https://doi.org/10.21856/j-PEP.2021.2.10

Most read articles by the same author(s)