A NOVEL MODEL OF TYPE 2 DIABETES AND DIABETIC NEPHROPATHY IN RATS

Non-genetic rat models of diabetic nephropathy are most commonly reproduced by using streptozotocin. However, administration of high doses of streptozotocin might have significant disadvantages such as severe hyperglycemia due to insulinopenic condition. Nevertheless, certain significant metabolic factors besides hyperglycemia, such as insulin resistance, obesity, dyslipidemia, and hypertension plays a crucial role in the onset and progression of diabetic nephropathy in type 2 diabetes mellitus. Hereby, we have described a novel model of type 2 diabetes and nephropathy in rats that is characterized by morphofunctional changes similar to relatively early stages of human diabetic nephropathy. Starting at 3 weeks after right-side nephrectomy, adult male Wistar rats were fed for 5 weeks the high-fat diet containing beef tallow and then successively received nicotinamide (230 mg/kg) and streptozotocin (65 mg/kg) intraperitoneally in 15-min interval. Control nondiabetic uninephrectomized rats received vehicle and were fed normal chow. With described model we observed the development of mild hyperglycemia, overweight, slight significant increase in insulin resistance, and dyslipidemia which resulted in a gradual decrease in renal function up to significant reduced creatinine clearance and elevated albuminuria, and confirmed diabetic nephropathy by validated electron and light microscopic morphological criteria at week 30 of the study.

крысы, негенетическая модель, сахарный диабет 2-го типа, диабетическая нефропатия, rats, non-genetic model, type 2 diabetes mellitus, diabetic nephropathy

1. Шестакова М.В, Дедов И.И. Сахарный диабет и хроническая болезнь почек. М.: Медицинское информационное агентство, 2009. с. 482

2. Байрашева В.К. Моделирование сахарного диабета и диабетической нефропатии в эксперименте. Современные проблемы науки и образования. 2015; 4

3. Tesch G.H, Allen T.J. Rodent models of streptozotocin-induced diabetic nephropathy. Nephrology (Carlton). 2007;12(3): 261-266.

4. Yamamoto H, Uchigata Y, Okamoto H. Streptozotocin and alloxan induce DNA strand breaks and poly(ADP-ribose) synthetase in pancreatic islets. Nature; 294:284-286.

5. Zhang M, Lv X, Li J, et al. The characterization of high-fat diet and multiple low-dose streptozotocin induced type 2 diabetes rat model. Exp. Diabetes Res. 2008; 2008:704045.

6. Danda R.S, Habiba N.M, Rincon-Choles H, et al. Kidney involvement in a nongenetic rat model of type 2 diabetes. Kidney Int. 2005; 68(6): 2562 - 2571.

7. Sugano M, Yamato H, Hayashi T, et al. High-fat diet in low-dose-streptozotocin-treated heminephrectomized rats induces all features of human type 2 diabetic nephropathy: a new rat model of diabetic nephropathy. Nutr. Metab. Cardiovasc. Dis. 2006;16(7):477-484.

8. Patel R, Shah P, Deshpande S, et al. Fructose diet and low dose streptozotocin treatment induces the development of diabetic nephropathy in rats. Orient. Pharm. Exp. Med. 2015;15: 305.

9. Байрашева В.К, Бабенко А.Ю, Чефу С.Г, и др. Нефропротективные свойства ингибитора ДПП-4 в условиях экспериментальной диабетической нефропатии. Современные проблемы науки и образования. 2015; 3

10. Ghasemi A, Khalifi S, Jedi S. Streptozotocinnicotinamideinduced rat model of type 2 diabetes (review). Acta Physiol. Hung. 2014; 101(4): 408-420.

11. Islam S, Choi H. Nongenetic model of type 2 diabetes: a comparative study. Pharmacology. 2007; 79: 243-249.

12. Спасов А. А, Воронкова М. П, Снигур Г.Л, и др. Экспериментальная модель сахарного диабета типа 2. Биомедицина. 2011; 3: 12-18

13. Khanra R, Dewanjee S, K Dua T, et al. Abroma augusta L. (Malvaceae) leaf extract attenuates diabetes induced nephropathy and cardiomyopathy via inhibition of oxidative stress and inflammatory response. J. Transl. Med. 2015; 13:6.

14. Peterson R.G, Jackson C.V, Zimmerman K, et al. Characterization of the ZDSD rat: a translational model for the study of metabolic syndrome and type 2 diabetes. J. Diabetes Res. 2015; 2015:487816.

15. Piepsz A, Collier F, Kinthaert J, et al. Effect of hyperfiltration on long-term follow-up of glomerular filtration rate in male Wistar rats. Pediatr. Nephrol. 1994; 8(6): 710-714.

16. Ekoé J.M, Rewers M, Williams R, et al. The Epidemiology of diabetes mellitus. 2nd Ed. UK: John Wiley & Sons Ltd, 2008. p. 720.

17. Bayrasheva V.K, Grineva E.N, Babenko A.Y, et al. Metformin and vildagliptin: from blood glucose lowering to nephroprotection. Eur. Heart J. 2015; 36 (suppl 1): P 436.