The experimental model of type 2 diabetes mellitus caused by a high-fat diet with low-dose streptozotocin in rats
https://doi.org/10.20538/1682-0363-2020-2-41-47
Abstract
Aim. To develop a pathogenetically reasonable model of type 2 diabetes with marked peripheral insulin resistance and relative insulin deficiency in rats using a high-fat diet and a single injection of streptozotocin in the low dose.
Materials and methods. Experiments were conducted on 16 outbred male rats. Type 2 diabetes model in experimental animals was achieved by feeding them with high-fat diet (55% of energy from fat) for 28 days followed by a single injection of streptozotocin (35 mg/kg). The serum glucose and insulin concentrations in rats were measured before streptozotocin administration and at the end of the experiment. To estimate insulin resistance, insulin tolerance test and glucose tolerance test were performed. Total protein, albumin, total and direct bilirubin, urea, uric acid, total cholesterol, high-density lipoproteins and low-density lipoproteins, and activity of alanine aminotransferase and aspartate aminotransferase were measured in the blood serum.
Results. A high-fat diet with a single injection of streptozotocin resulted in lipid and protein metabolism disorders and peripheral tissues insulin resistance in experimental animals. Basal insulin levels did not change against the backdrop of high glucose level.
Conclusions. These results indicate that feeding rats with a high-fat diet (55% of calories from fats) and a single administration of streptozotocin at a low dose (35 mg/kg) reproduce general pathological processes of type 2 diabetes. This model can be used to study the pathogenesis of type 2 diabetes as well as to investigate the effect of potential hypoglycemic agents.
About the Authors
O. A. KaydashRussian Federation
2, Mosсow Trakt, Tomsk, 634050, Russian Federation
V. V. Ivanov
Russian Federation
2, Mosсow Trakt, Tomsk, 634050, Russian Federation
2, Mosсow Trakt, Tomsk, 634050, Russian Federation
A. I. Vengerovsky
Russian Federation
2, Mosсow Trakt, Tomsk, 634050, Russian Federation
E. E. Buyko
Russian Federation
30, Lenina Av., Tomsk, 634050, Russian Federation
I. A. Schepetkin
Russian Federation
30, Lenina Av., Tomsk, 634050, Russian Federation
960, Technology Blvd., Bozeman, 59715, United States of America
References
1. Cho N.H., Shaw J.E., Karuranga S., Huang Y., Da R.F.J., Ohlrogge A.W., Malanda B. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Research and Clinical Practice. 2018; 138: 271–281. DOI: 10.1016/j.diabres.2018.02.023.
2. Lenzen S. The mechanisms of alloxan-and streptozotocin-induced diabetes. Diabetologia. 2008; 51 (2): 216–226. DOI 10.1007/s00125-007-0886-7.
3. Guo X.X., Wang Y., Wang K., Ji B.P., Zhou F. Stability of a type 2 diabetes rat model induced by high-fat diet feeding with low-dose streptozotocin injection. Journal of Zhejiang University-Science B. 2018; 19 (7): 559–569. DOI: 10.1631/jzus.B1700254.
4. Premilovac D., Gasperini R.J., Sawyer S., West A., Keske M.A., Taylor B.V., Foa L. A new method for targeted and sustained induction of type 2 diabetes in rodents. Scientific Reports. 2017; 7 (1): 14158. DOI: 10.1038/s41598-017-14114-4.
5. Kapilevich L.V., Zakharova A.N., Dyakova E.Yu., Kironenko T.A., Milovanova K.G., Kalinnikova J.G., Chibalin A.V. Mice experimental model of diabetes mellitus type ii based on high fat diet. Bulletin of Siberian Medicine. 2019; 18 (3): 53–61. DOI: 10.20538/1682-0363-2019-3-53–61.
6. Skovsø S. Modeling type 2 diabetes in rats using high fat diet and streptozotocin. Journal of Diabetes Investigation. 2014; 5 (4): 349–358. DOI: 10.1111/jdi.12235.
7. Gheibi S., Kashfi K., Ghasemi A. A practical guide for induction of type-2 diabetes in rat: Incorporating a high-fat diet and streptozotocin. Biomed Pharmacotherapy. 2017; 95: 605–613. DOI: 10.1016/j.biopha.2017.08.098.
8. Monzillo L.U., Hamdy O. Evaluation of insulin sensitivity in clinical practice and in research settings. Nutrition Reviews. 2003; 61 (12): 397–412. DOI: 10.1301/nr.2003.dec.397-412.
9. Kumar Sharma A., Bharti S., Ojha S., Bhatia J., Kumar N., Ray R., Kumari S, Singh Arya D. Up-regulation of PPARγ, heat shock protein-27 and -72 by naringin attenuates insulin resistance, β-cell dysfunction, hepatic steatosis and kidney damage in a rat model of type 2 diabetes. British Journal of Nutrition. 2011; 106 (11): 1713– 1723. DOI: 10.1017/S000711451100225X
Review
For citations:
Kaydash O.A., Ivanov V.V., Vengerovsky A.I., Buyko E.E., Schepetkin I.A. The experimental model of type 2 diabetes mellitus caused by a high-fat diet with low-dose streptozotocin in rats. Bulletin of Siberian Medicine. 2020;19(2):41-47. https://doi.org/10.20538/1682-0363-2020-2-41-47