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Updated: Aug 16, 2026
Assessment of Kidney Function in Mouse Models of Glomerular Disease
Published on: June 30, 2018
Standardization of type 1 and type 2 diabetic nephropathy models in rats: Assessment and characterization of
Aakruti A Kaikini1, Divya Dhodi1, Suraj Muke1
1Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Mumbai, Maharashtra, India.
Background:
Diabetes mellitus and its complications, such as nephropathy, represent a global burden. Recent research focuses on developing drugs that specifically target the pathogenesis of diabetic nephropathy rather than merely treating hyperglycemia. Rodent models of animal disease are integral in drug discovery and represent an obligatory regulatory requirement.
Aim:
The aim of this study was to develop and standardize rat models of type 1 and type 2 diabetic nephropathy, resembling characteristics of human clinical condition.
Materials And Methods:
Rats were administered streptozotocin (STZ) 50 mg/kg intraperitoneally (i.p.), and STZ 50 mg/kg i.p. + nicotinamide (NA) 110 mg/kg i.p., for induction of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), respectively. Metabolic parameters (body weight, feed and water intake, blood glucose, serum insulin, oral glucose tolerance test, intraperitoneal insulin tolerance test, and indices of insulin sensitivity) were evaluated to characterize the symptoms of T1DM and T2DM. Renal damage was confirmed by the estimation of renal function biomarkers, kidney antioxidant status, kidney hypertrophy index, and histopathology.
Results:
STZ and STZ + NA administration increased blood glucose levels significantly. Metabolic parameters indicated that administration of STZ resulted in clinical features of human T1DM, whereas STZ + NA rats resembled human T2DM. STZ- and STZ + NA-treated rats developed diabetic nephropathy in 4 weeks, indicated by altered levels of renal function markers, increased kidney hypertrophy index, increased renal oxidative stress, and altered tissue architecture. The study proposes reproducible and cost-effective rat models for both T1DM- and T2DM-induced diabetic nephropathy characterized by stable metabolic features and typical renal lesions.
Insights
Researchers developed reproducible rat models for type 1 and type 2 diabetic nephropathy. These models mimic human diabetic kidney disease, aiding drug discovery for this global health burden.
Area of Science:
- Nephrology
- Endocrinology
- Pharmacology
Background:
- Diabetic nephropathy is a major complication of diabetes mellitus, posing a significant global health challenge.
- Current research prioritizes targeted therapies for diabetic nephropathy pathogenesis over simple hyperglycemia management.
- Rodent models are crucial for drug discovery and regulatory approval in diabetes research.
Purpose of the Study:
- To establish and validate rat models for type 1 and type 2 diabetic nephropathy.
- To ensure these models accurately reflect human clinical diabetic kidney disease characteristics.
Main Methods:
- Type 1 diabetes mellitus induced using streptozotocin (STZ).
- Type 2 diabetes mellitus induced using STZ combined with nicotinamide (NA).
- Evaluated metabolic parameters, renal function, oxidative stress, and histopathology to confirm disease induction and characteristics.
Main Results:
- STZ and STZ+NA treatments significantly elevated blood glucose levels.
- STZ-induced rats exhibited type 1 diabetes mellitus features, while STZ+NA rats mimicked type 2 diabetes mellitus.
- Both models developed diabetic nephropathy within 4 weeks, showing altered renal biomarkers, oxidative stress, and tissue damage.
Conclusions:
- Successfully developed reproducible and cost-effective rat models for type 1 and type 2 diabetic nephropathy.
- These models exhibit stable metabolic profiles and characteristic renal lesions, suitable for preclinical drug development.
- Validated models provide a valuable tool for advancing therapies for diabetic kidney disease.
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