Animal Models of Diabetes-Associated Renal Injury

Abstract

Diabetic nephropathy (DN) is the main factor leading to end-stage renal disease (ESRD) and subsequent morbidity and mortality. Importantly, the prevalence of DN is continuously increasing in developed countries. Many rodent models of type 1 and type 2 diabetes have been established to elucidate the pathogenesis of diabetes and examine novel therapies against DN. These models are developed by chemical, surgical, genetic, drug, and diet/nutrition interventions or combination of two or more methods. The main characteristics of DN including a decrease in renal function, albuminuria and mesangiolysis, mesangial expansion, and nodular glomerulosclerosis should be exhibited by an animal model of DN. However, a rodent model possessing all of the abovementioned features of human DN has not yet been developed. Furthermore, mice of different genetic backgrounds and strains show different levels of susceptibility to DN with respect to albuminuria and development of glomerular and tubulointerstitial lesions. Therefore, the type of diabetes, development of nephropathy, duration of the study, cost of maintaining and breeding, and animals’ mortality rate are important factors that might be affected by the type of DN model. In this review, we discuss the pros and cons of different rodent models of diabetes that are being used to study DN.

α-Ketoglutarate Upregulates Collecting Duct (Pro)renin Receptor Expression, Tubular Angiotensin II Formation, and Na+ Reabsorption During High Glucose Conditions

“…In the present study, we have used a model of early diabetic conditions to trigger with no gross kidney damage. Six days of hyperglycemia was chosen because longer periods implicate nephropathy and further damage (e.g., including collagen deposition in glomerular, tubulointerstitial, and perivascular areas) in rat ( 37 ) and mice kidneys after 3 and 5 weeks post-STZ injection, respectively ( 38 ). Furthermore, it is possible that ML treatment in STZ-induced diabetic mice for a longer period of time would result in further protection against PRR augmentation and PRR-related signaling pathways related to fibrosis; however, longer treatments (>6 days of single STZ dose) showed structural evidence of acute tubular necrosis in mice ( 39 ).…”

The effect of co-enzyme Q10 and N-acetylcysteine on biochemical parameters and oxidative stress in rats subjected to alloxan induced diabetic nephropathy

“…12 The diabetogenic effects of ALX resulting in necrosis of β-cells are mediated via chronic hyperglycemia and subsequent production of ROS culminates in diabetic renal damage and T1DN. 13,14 In the present study, single injection of ALX (130 mg/kg, i.p.) resulted in hyperglycemia in rats which further resulted in renal dysfunction as shown by increased serum creatinine, decreased total protein and albumin with declined creatinine clearance and increased UAER in comparison to the control rats.…”

Diffusion Tensor Imaging in Rat Models of Preclinical Diabetic Nephropathy: A Preliminary Study

“…Second, this study did not analyze the correlation between DTI parameters and pathological damage. Thirdly, there may be some measurement errors because ROIs were drawn manually, and STZ may has certain nephrotoxicity, which may cause acute kidney injury in rats (27), and interfered with renal changes.…”