Long-term renal changes in the Goto-Kakizaki rat, a model of lean type 2 diabetes

• Published in: Nephrology, dialysis, transplantation Vol. 19; no. 5; pp. 1092 - 1097
• Main Authors: Schrijvers, Bieke F., De Vriese, An S., Van de Voorde, Johan, Rasch, Ruth, Lameire, Norbert H., Flyvbjerg, Allan
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-05-2004
• Subjects: Albuminuria; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Associated diseases and complications; basement membrane thickness; Biological and medical sciences; Blood Glucose - metabolism; Blood Pressure; Creatinine - metabolism; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - physiopathology; Diabetes. Impaired glucose tolerance; Disease Models, Animal; Emergency and intensive care: renal failure. Dialysis management; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Feeding Behavior; glomerular volume; Goto–Kakizaki rat; Intensive care medicine; kidney; Kidney - anatomy & histology; Kidney - pathology; Kidney - physiopathology; Medical sciences; mesangium; Metabolic Clearance Rate; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Organ Size; Rats; Rats, Mutant Strains; Rats, Wistar; Renal failure; Kidney disease; Type 2 diabetes; Urinary system disease; Goto-Kakizaki rat; Rat; Hemodialysis; Rodentia; kidney: mesangium; glomerular volume; Change; Long term; Basement membrane; Thickness; Extrarenal dialysis; albuminuria; Vertebrata; Mammalia; Volume; Animal; Renal failure; basement membrane thickness; Models
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gfh107

Background. Type 2 diabetes has become the single most frequent cause of end-stage renal disease. The Goto–Kakizaki rat is currently used as a model for lean type 2 diabetes, but its renal changes have not been fully characterized. We investigated long-term functional and structural renal changes in the Goto–Kakizaki rat to evaluate if this animal model resembles the changes observed in human diabetic kidney disease. Methods. Urinary albumin excretion, creatinine clearance and blood pressure were measured at the age of 2, 8 and 14 months in 12 female Goto–Kakizaki rats and 10 female, non-diabetic Wistar rats. To study kidney morphology, kidney weight, glomerular volume, basement membrane thickness, mesangial fraction and total mesangial volume were determined at 14 months. Results. Urinary albumin excretion rose progressively over time in both groups, but was significantly higher in Goto–Kakizaki rats than in Wistar rats. Creatinine clearance decreased over time in Goto–Kakizaki rats but not in Wistar rats. Blood pressure was in the normotensive range in all animals throughout the study. Kidney weight, glomerular volume, basement membrane thickness, mesangial fraction and total mesangial volume were significantly higher in Goto–Kakizaki rats than in Wistar rats. Body weight and blood glucose levels were higher, whereas serum insulin levels were not different or lower in Goto–Kakizaki rats compared with Wistar rats. Conclusion. The Goto–Kakizaki rat is a lean, hyperglycaemic, euinsulinaemic, normotensive experimental model of type 2 diabetes with robust functional and structural renal changes.