ECE2017 Guided Posters Diabetes & complications 2 (10 abstracts)
Non-genetic rat model of nephropathy in type 2 diabetes with attenuated streptozotocin-induced tubular alteration
Valentina Bayrasheva 1, , Alina Babenko 1, , Ivan Pchelin 3 , Anna Arefjeva 2 , Svetlana Chefu 1, , Ivan Shatalov 4 , Yurii Dmitriev 1 , Alexandra Ivanova 3, , Pavel Andoskin 1 , Parvis Aliev 2 & Elena Grineva 1,
1Federal Almazov North-West Medical Research Centre, Saint Petersburg, Russia; 2Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russia; 3Saint Petersburg State University, Saint Petersburg, Russia; 4Saint Petersburg National Research University of Information, Technologies, Mechanics and Optics, Saint Petersburg, Russia; 5Komarov Botanical Institute of the Russian Academy of Sciences, Saint Petersburg, Russia.
Non-genetic animal models of diabetic nephropathy (DN) are most commonly reproduced by using streptozotocin (STZ) which preferentially gets into β-cells via GLUT2 transporters. However, STZ administration results in nephrotoxic effects as well, due to expression of GLUT2 by renal tubular epithelial cells. We hypothesized that nicotinamide (NA), which is considered to attenuate the severity of STZ-induced β-cell damage, could also prevent tubular alteration. Starting at 3 weeks after unilateral nephrectomy, thirty adult male Wistar rats were fed the high-fat diet for 5 weeks and then successively received either NA (230 mg/kg) and STZ (65 mg/kg, NA-STZ-group) or STZ in a low dose (40 mg/kg, LD-STZ-group) intraperitoneally in 15-min interval. Control nondiabetic uninephrectomized rats received vehicle and were fed normal chow (C-group). 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, NA-STZ-injected rats showed overweight (328.9±22.7 g (NA-STZ) vs 285.4±20.5 g (C)), mild hyperglycemia (HbA1c 5.39±0.24% vs 3.6±0.29%), significant increase in insulin resistance (HOMA-IR 3.2±0.39 vs 1.93±0.29),and dyslipidemia (total cholesterol 2.89±0.25 mmol/l vs 1.55±0.35; triglycerides 1.05±0.18 mmol/l vs 0.57±0.1), P<0.05 each, that were observed until the end of the study. At 20 weeks, development of early stage of DN was confirmed by glomerular basement membrane thickness, gradual decline in creatinine clearance, and mild albuminuric status (478.4±63.3 μ/24 h vs 35.8±3.6 μ/24 h), with progression by week 30, when light microscopic features of DN were observed. Morphofunctional renal changes in NA-STZ appeared to be more pronounced than those in LD-STZ despite lower levels of KIM-1 and NGAL (2535.8±303.9 ng/24 h (LD-STZ) at week 30) vs 1704.4±444.7 ng/24 h in NA-STZ, P=0.037. We have described a model of type 2 diabetes and DN with attenuated STZ-induced tubular alteration in rats that is characterized by stable metabolic disorders and renal morphofunctional changes similar to relatively early stages of human DN.
Volume 49
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more