title: Uninephrectomized High-Fat-Fed Nicotinamide-Streptozotocin-Induced Diabetic Rats: A Model for the Investigation of Diabetic Nephropathy in Type 2 Diabetes.
abstract: 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 after uninephrectomy, adult male Wistar rats were fed five-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 significantly 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.
authors.affiliation: Institute of Endocrinology, Federal Almazov North-West Medical Research Centre, Saint Petersburg, Russia; Department for Pathophysiology, Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russia.
authors.forename: Valentina K
authors.identifier: 0000-0002-1180-3365
authors.initials: VK
authors.lastname: Bayrasheva
authors.affiliation: Institute of Endocrinology, Federal Almazov North-West Medical Research Centre, Saint Petersburg, Russia.
authors.forename: Alina Yu
authors.identifier: 0000-0002-0559-697X
authors.initials: AY
authors.lastname: Babenko
authors.affiliation: Research Institute of Nephrology, Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russia.
authors.forename: Vladimir A
authors.identifier: 0000-0002-7179-5520
authors.initials: VA
authors.lastname: Dobronravov
authors.affiliation: Institute of Experimental Medicine, Federal Almazov North-West Medical Research Centre, Saint Petersburg, Russia.
authors.forename: Yuri V
authors.initials: YV
authors.lastname: Dmitriev
authors.affiliation: Department for Pathophysiology, Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russia; Institute of Experimental Medicine, Federal Almazov North-West Medical Research Centre, Saint Petersburg, Russia.
authors.forename: Svetlana G
authors.initials: SG
authors.lastname: Chefu
authors.affiliation: Saint Petersburg State University, Saint Petersburg, Russia.
authors.forename: Ivan Yu
authors.initials: IY
authors.lastname: Pchelin
authors.affiliation: Saint Petersburg State University, Saint Petersburg, Russia; Komarov Botanical Institute of the Russian Academy of Sciences, Saint Petersburg, Russia.
authors.forename: Alexandra N
authors.identifier: 0000-0002-7034-0962
authors.initials: AN
authors.lastname: Ivanova
authors.affiliation: Institute of Endocrinology, Federal Almazov North-West Medical Research Centre, Saint Petersburg, Russia.
authors.forename: Alekber A
authors.initials: AA
authors.lastname: Bairamov
authors.affiliation: Department of Statistical Modelling, Mathematics and Mechanics Faculty, Saint Petersburg State University, Saint Petersburg, Russia.
authors.forename: Nina P
authors.initials: NP
authors.lastname: Alexeyeva
authors.affiliation: Saint Petersburg National Research University of Information, Technologies, Mechanics and Optics, Saint Petersburg, Russia.
authors.forename: Ivan S
authors.initials: IS
authors.lastname: Shatalov
authors.affiliation: Institute of Endocrinology, Federal Almazov North-West Medical Research Centre, Saint Petersburg, Russia.
authors.forename: Elena N
authors.identifier: 0000-0003-0042-7680
authors.initials: EN
authors.lastname: Grineva
mesh_terms: D000818:Animals; D001786:Blood Glucose; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000503:physiopathology*; D059305:Diet, High-Fat; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D009392:Nephrectomy / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001786:Blood Glucose