Journal
JOURNAL OF DIABETES RESEARCH
Volume 2016, Issue -, Pages -Publisher
HINDAWI LTD
DOI: 10.1155/2016/8317850
Keywords
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Funding
- Russian Foundation for Basic Research [15-0408138]
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Type 2 diabetes (DM2) could be reproduced in rats with alimentary obesity by using low doses of streptozotocin (LD-STZ) aswell 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 (40mg/kg) or NA (230mg/kg) followed by STZ (65mg/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 ofDM2 with DN characterized by stable metabolic disorders, typical renal lesions, and lower levels of tubular injury markers as compared to LD-STZ-induced diabetes.
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