Research Article Uninephrectomized High-Fat-Fed Nicotinamide-Streptozotocin-Induced Diabetic Rats: A Model for the Investigation of Diabetic Nephropathy in Type 2 Diabetes Valentina K. Bayrasheva, 1,2 Alina Yu. Babenko, 1 Vladimir A. Dobronravov, 3 Yuri V. Dmitriev, 4 Svetlana G. Chefu, 2,4 Ivan Yu. Pchelin, 5 Alexandra N. Ivanova, 5,6 Alekber A. Bairamov, 1 Nina P. Alexeyeva, 7 Ivan S. Shatalov, 8 and Elena N. Grineva 1 1 Institute of Endocrinology, Federal Almazov North-West Medical Research Centre, Saint Petersburg, Russia 2 Department for Pathophysiology, Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russia 3 Research Institute of Nephrology, Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russia 4 Institute of Experimental Medicine, Federal Almazov North-West Medical Research Centre, Saint Petersburg, Russia 5 Saint Petersburg State University, Saint Petersburg, Russia 6 Komarov Botanical Institute of the Russian Academy of Sciences, Saint Petersburg, Russia 7 Department of Statistical Modelling, Mathematics and Mechanics Faculty, Saint Petersburg State University, Saint Petersburg, Russia 8 Saint Petersburg National Research University of Information, Technologies, Mechanics and Optics, Saint Petersburg, Russia Correspondence should be addressed to Valentina K. Bayrasheva; bayrasheva med@mail.ru Received 17 June 2016; Revised 30 October 2016; Accepted 8 November 2016 Academic Editor: Bernard Portha Copyright © 2016 Valentina K. Bayrasheva et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Type 2 diabetes (DM2) could be reproduced in rats with alimentary obesity by using low doses of streptozotocin (LD-STZ) as well as STZ in high doses with preliminary nicotinamide (NA) administration. However, STZ could induce tubulotoxicity. Aim. To develop rat model of DN in NA-STZ-induced DM2 and compare it with LD-STZ-model in order to choose the most relevant approach for reproducing renal glomerular and tubular morphofunctional diabetic changes. Starting at 3 weeks afer uninephrectomy, adult male Wistar rats were fed fve-week high-fat diet and then received intraperitoneally either LD-STZ (40 mg/kg) or NA (230 mg/kg) followed by STZ (65 mg/kg). Control uninephrectomized vehicle-injected rats received normal chow. At weeks 10, 20, and 30 (the end of the study), metabolic parameters, creatinine clearance, albuminuria, and urinary tubular injury markers (NGAL, KIM-1) were evaluated as well as renal ultrastructural and light microscopic changes at weeks 20 and 30. NA-STZ-group showed higher reproducibility and stability of metabolic parameters. By week 10, in NA-STZ-group NGAL level was signifcantly lower compared to LD-STZ-group. By week 30, diabetic groups showed early features of DN. However, morphofunctional changes in NA-STZ- group appeared to be more pronounced than those in STZ-group despite lower levels of KIM-1 and NGAL. We proposed a new rat model of DM2 with DN characterized by stable metabolic disorders, typical renal lesions, and lower levels of tubular injury markers as compared to LD-STZ-induced diabetes. 1. Introduction Appropriate experimental animal models of diabetic neph- ropathy (DN) are essential for studying its pathogenesis and diferent strategies of nephroprotection. Te development of DN in type 2 diabetes (DM2) in most cases is triggered not only by hyperglycemia but also by other pathogenic factors associated with obesity, insulin resistance, hypertension, and dyslipidemia [1, 2]. In order to extrapolate relevantly preclinical data into clinical reality, animal models of DN Hindawi Publishing Corporation Journal of Diabetes Research Volume 2016, Article ID 8317850, 18 pages http://dx.doi.org/10.1155/2016/8317850