Relevance. When modeling experimental type 2 diabetes mellitus (T2DM), various schools and research groups receive significant variability in tissue changes, which is difficult to compare and extrapolate as a specific pathogenic or pharmacological effect. The lack of standard operating procedures agreed upon in the scientific community greatly complicates the interpretation of the result. Therefore, the creation of a uniquely pathogenetic animal model of CD2 in animals is an urgent task.
Objective. Determination of the complex of exogenous effects for the most efficient reproduction of the experimental model of T2DM in rats and the pathogenetic justification of the changes in the body to study the central mechanisms of homeostasis regulation and their pharmacological correction.
Materials and methods. T2DM was model in rats by feeding a high-fat diet (HFD) with additional streptozotocin induction. The model was evaluated by anthropometric measurements, studies of biochemical parameters, an insulin tolerance test, analysis of the spectrum of fatty acids in the composition of tissues. Statistical data processing was performed with using the IBM SPSS Statistics 23.
Results. The obtained data were compared with our studies of the lipid metabolism of patients with varying degrees of diabetic retinopathy on the background of T2DM and analysis of the information content of biochemical markers to assess lipid metabolic disturbances on the background of hyperglycemia in patients. It was found that the simulation in rats of experimental T2DM by a food load of HFD (45%) + fructose 20% for 3 months followed by a single induction of streptozotocin (25 mg/kg) causes changes in lipid and carbohydrate metabolism in animals similar changes which are in the human with a diagnosed long-term diabetes and the development of microvascular complications.
Conclusion. We determined the optimal combination of effects and developed a consistent experimental load scheme that allows us to obtain a symptom model of type 2 diabetes in an animal experiment. Using the diagnostic algorithm, which includes physiological and laboratory methods, the degree of damage to organs and systems was determined, a comparison was made with the level of metabolic disorders in patients with T2DM and people without diabetes. The given model is a pathogenetically grounded approach for further study of the central mechanisms of homeostasis regulation and their pharmacological correction
Bayrasheva V.K. [Modeling of diabetes mellitus and diabetic nephropathy in the experiment] // Modern problems of science and education. 2015; 4. [in Russian]. URL: http://www.science-education.ru/ru/article/view?id=21024
Kravchuk E.N., Galagudza M.M. [Experimental models of metabolic syndrome] // Arterial hypertension. 2014; 20 (5): 377-83. [in Russian]. URL: https://cyberleninka.ru/article/n/eksperimentalnye-modeli-metabolicheskogo-sindroma
Leshchenko D.V., Kostyuk, N.V., Egorova, E.N., Belyakova, M. B., Minyaev, M. V., Petrova, M. B. [Modeling of metabolic syndrome in animals by the action of chemical agents and diet] // Bulletin of TvSU. Series: Chemistry (2). 2015: P. 141-152. ISSN 1995-0152. [in Russian]. URL: http://eprints.tversu.ru/5385/
Markhon N.O., Mamchur V.I., Zhilyuk V.I., Levykh A.E. Comparative analysis of experimental approaches in the reproduction of metabolic syndrome // Bulletin of problems in biology and medicine. 2015; 1: 156-62. [in Ukrainian]. URL: http://nbuv.gov.ua/UJRN/Vpbm_2015_1_33.
Natrus L.V., Ryzhko I.M., Chernovol P.A., Bryuzgina T.S. Patent 125810 UA, IPC G01N 33/49 (2006.01) B01D15 / 08 (2006.01) [Method for the evaluation of tissue damage mechanisms in type 1 experimental diabetes mellitus in rats] / Owner O.O. Bogomolets National Medical University of the Ministry of Health of Ukraine.- u 201709175; stated on 09/18/2017; published March 12, 2018, Bul. No. 15, 2018 [in Ukrainian].
Osadchuk Yu.S., Chaikovsky Yu.B., Natrus L.V., Bryuzgina T.S. [Features of changes in fatty acid composition of tissues in different models of type 1 experimental diabetes] // Medical Science of Ukraine. 2018; 14 (3-4): 13-22. [in Ukrainian]. URL: https://doi.org/10.32345/2664-4738.3-4.2018.02
Mouse Metabolic Phenotyping Center (MMPC). - https://www.mmpc.org/shared/document.aspx?id=272&docType=Protocol
Spasov A.A., Babkov D.A., Muleeva D.R., & Mayka O.Yu. [Modeling type 2 diabetes mellitus in rats on a high-fat diet with streptozotocin induction] // Bulletin of the Volgograd State Medical University. 2017; 1 (61): 30-2. [in Russian]. URL: https://cyberleninka.ru/article/n/modelirovanie-saharnogo-diabeta-tipa-2-u-krys-na-vysokozhirovoy-diete-s-induktsiey-streptozototsinom
Stefanov OV (ed.) [Preclinical Drug Research. Guidelines] – Kyiv: Avicenna, 2001. 528 p. [in Ukrainian].
Tvorogova M.G., Yaskova K.N., Mychka V.B., Chazova I.E. [Insulin resistance and methods of its diagnostics] // Laboratory medicine [in Russian]. URL: http://www.ramld.ru/articles/article.php?id=20
Ayala J.E., Samuel V.T., Morton G.J. et al. Standard operating procedures for describing and performing metabolic tests of glucose homeostasis in mice // Dis Model Mech. 2010; 3 (9-10): 525-34. https://doi.org/10.1242/dmm.006239
Bykhovets M. Information value of biochemical markers for evaluation of lipid dysmetabolism secondary to hyperglycaemia in patients with diabetic retinopathy and type 2 diabetes mellitus // East European Scientific Journal (Warsaw, Poland) 2019; 9 (49)/1: 19-25. https://eesa-journal.com/wp-content/uploads/EESA_september_part_1.pdf
Bykhovets M.Y., Rykov S.O., Natrus L.V. [Features of the lifestyle as a factor of the risk of development and progression of diabetic retinopathy in patients with diabetes mellitus of 2 types] // Arkhiv oftalʹmolohiyi Ukrayiny. 2019; 7 (1): 54-61. DOI: http://dx.doi.org/10.22141/2309-8220.127.116.119.163000
Koehrer P., Saab S., Berdeaux O., Isaïco R., Grégoire S., et al. Erythrocyte Phospholipid and Polyunsaturated Fatty Acid Composition in Diabetic Retinopathy // PLOS ONE. 2014; 9 (9): e106912. https://doi.org/10.1371/journal.pone.0106912
López M., Ríos-Silva M., Huerta M. Effects of Moringa oleifera leaf powder on metabolic syndrome induced in male Wistar rats: a preliminary study // The Journal of international medical research. 2018; 46 (8): 3327-36. doi:10.1177/0300060518781726.
Natrus L.V. Changes in activity of the hypothalamic neurons in response to physiological fluctuations of the homeostasis constants // Fiziolohichnyǐ zhurnal 2006; 52 (3): 57-63 https://www.ncbi.nlm.nih.gov/pubmed/16909757.
This work is licensed under a Creative Commons Attribution 4.0 International License.