A novel mouse model of diabetes mellitus using unilateral nephrectomy (original) (raw)
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Scientific Reports, 2018
Diabetic nephropathy (DN) is the leading cause of chronic kidney disease. Animal models are essential tools for designing new strategies to prevent DN. C57Bl/6 (B6) mice are widely used for transgenic mouse models, but are relatively resistant to DN. This study aims to identify the most effective method to induce DN in a type 1 (T1D) and a type 2 diabetes (T2D) model in B6 mice. For T1D-induced DN, mice were fed a control diet, and randomised to streptozotocin (STZ) alone, STZ+unilateral nephrectomy (UNx), or vehicle/sham. For T2D-induced DN, mice were fed a western (high fat) diet, and randomised to either STZ alone, STZ+UNx, UNx alone, or vehicle/sham. Mice subjected to a control diet with STZ +UNx developed albuminuria, glomerular lesions, thickening of the glomerular basement membrane, and tubular injury. Mice on control diet and STZ developed only mild renal lesions. Furthermore, kidneys from mice on a western diet were hardly affected by diabetes, UNx or the combination. We co...
Journal of diabetes research, 2016
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 sh...
Effect of unilateral nephrectomy on renal function of diabetic rats
Histology and histopathology, 2004
Glomerular alterations of experimental diabetes mellitus are observed in animals submitted to a reduction in renal mass, suggesting that some mechanisms responsible for the progression of renal disease are common. The aim of this study was to investigate the effect of nephrectomy on the renal function and morphology of diabetic rats. Male Wistar rats were divided into 4 groups: control (C), n=8; diabetic (DM), n=8; non-diabetic nephrectomized (Nx), n=8; (DMNx), n=9. DM was induced by streptozotocin (65 mg/Kg), and animals were treated with insulin. After 12 weeks, the glomerular filtration rate (GFR), renal plasma flow (RPF) and mean arterial pressure (MAP) were evaluated in unanaesthetized animals. Glomerular volume (GV), glomerular sclerosis index (GSI), mesangial volume density (Vvmes) and glomerular capillary surface density (Svcap) were also evaluated. Results show that kidney weight increased in Nx groups, being higher in DMNx. GFR was higher in Nx groups as was RPF, being hig...
Journal of Diabetes Research, 2014
The Spontaneously Diabetic Torii (SDT) fatty rat is a new model for obese type 2 diabetes. The aim of the present study was to investigate the effect of 1/2 nephrectomy (Nx) on renal function and morphology and on blood pressure in SDT fatty rats. Male SDT fatty rats underwent 1/2 Nx or a sham operation (Sham). Subsequently, animals were studied with respect to renal function and histological alterations. Induction of 1/2 Nx in SDT fatty rats led to functional and morphological damage to the remnant kidney and to hypertension, which are considered main characteristics of chronic kidney disease, at a younger age compared with the sham group. In conclusion, the SDT fatty rat is useful in investigations to elucidate the pathogenesis of human diabetic nephropathy and in new drug discovery.
Streptozotocin-induced diabetic nephropathy in rats 2005
The role of inflammatory cytokines in the pathogenesis of diabetic nephropathy has been studied in streptozotocin-induced diabetic rats. Rat kidneys were examined by light and electron microscopy and kidney homogenates were also analyzed by Western blot and flow cytometry for the expression of markers of inflammation namely, CD4C and CD8C T cells, macrophages, MHC classes I and II, the proinflammatory cytokines tumor necrosis factor-a, interferon-g and nitric oxide (NO). Light and electron microscope examination revealed infiltration of mononuclear cells throughout the renal parenchyma, with the glomeruli being more severely affected especially at 8 months after disease induction. Western blot and flow cytometric analyses revealed the infiltrating cells to be CD4C T cells, CD8C T cells and macrophages. Western blot analyses also revealed increased expression of the proinflammatory and Th1 cytokines tumor necrosis factor-a, interferon-g as well as nitric oxide. Using flow cytometry, we have shown that the difference in expression of CD4C T cells in control and diabetic kidneys is more significant at 1 month than at 8 months, while expression of CD8C T cells is more significant at 8 months. We speculate therefore that diabetic nephropathy is probably initiated and driven by a Th1 process. CD8C T cells, however, become more significant at later stages of the disease when tissue loss is evident. Since NO induction also occurs only after 8 months, we hypothesize that NO might be significant for the later stages of the disease. Our data implicate inflammation in the pathogenesis of diabetic nephropathy in view of the overexpression of the proinflammatory cytokines TNF-a and IFN-g and the cells that secrete them in the early and late phases of the disease.
Journal of Cellular Physiology, 2008
We have previously found progressive diabetic nephropathy in inducible cAMP early repressor (ICER Ig) transgenic (Tg) mice. The ICER Ig Tg mouse is an interesting model of sustained hyperglycemia due to its low production of insulin and insulin-producing b cells. Here in a longitudinal study we further analyzed diabetic nephropathy and structural and functional alterations in other organs, comparing our model with streptozotocin (STZ)-diabetic model mice. The high-dose STZ-diabetic model showed marked variation in blood glucose levels and severe toxicity of STZ in the liver and kidney. The low-dose STZ-diabetic model showed less toxicity, but the survival rate was very low. STZ-diabetic mice had much more variation of glomerular hypertrophy and sclerosis. Furthermore, non-specific toxicity of STZ or insulin injections to maintain optimal blood glucose levels might have another effect upon the diabetic renal changes. In contrast, ICER Ig Tg mice exhibited a stable and progressive phenotype of diabetic kidney disease solely due to chronic hyperglycemia without other modulating factors. Thus, ICER Ig Tg mouse has advantages for examining diabetic renal disease, and offers unique and very different perspectives compared to STZ model.
Nigerian Journal of Pharmaceutical Research
Background: Diabetes mellitus is a metabolic disorder which leads to complications that affect the heart, kidney, liver and other vital organs. Most reports on diabetes have focused on diabetes induction using male rat models in short term studies.Objective: Here, we described the induction of diabetes in female rat and the complications of diabetes following long term hyperglycemia in female Wistar rats.Method: Rats were assigned into two groups: control (n=10) and diabetic (n=10). The latter was administered a single (50mg/Kg body weight) intraperitoneal injection of streptozotocin. Bodyweight and blood glucose were assessed for 14 weeks, after which the animals were sacrificed and biochemical and morphology parameters of the liver, kidney and heart were determined.Results: Diabetic rats showed continuous emaciation post STZ induction. The glycated haemoglobin, protein level, lipid profile, liver and kidney function markers were significantly different (p<0.05) from the control...
Mouse Models of Diabetes, Obesity and Related Kidney Disease
PloS one, 2016
Multiple rodent models have been used to study diabetic kidney disease (DKD). The purpose of the present study was to compare models of diabetes and obesity-induced metabolic syndrome and determine differences in renal outcomes. C57BL/6 male mice were fed either normal chow or high fat diet (HFD). At postnatal week 8, chow-fed mice were randomly assigned to low-dose streptozotocin (STZ, 55 mg/kg/day, five consecutive days) or vehicle control, whereas HFD-fed mice were given either one high-dose of STZ (100 mg/kg) or vehicle control. Intraperitoneal glucose tolerance tests were performed at Week 14, 20 and 30. Urinary albumin to creatinine ratio (ACR) and serum creatinine were measured, and renal structure was assessed using Periodic Acid Schiff (PAS) staining at Week 32. Results showed that chow-fed mice exposed to five doses of STZ resembled type 1 diabetes mellitus with a lean phenotype, hyperglycaemia, microalbuminuria and increased serum creatinine levels. Their kidneys demonstr...