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


CONCLUSIONS
The Goto-Kakizaki rat is a lean, hyperglycaemic, euinsulinaemic, normotensive experimental model of type 2 diabetes with robust functional and structural renal changes.
Medical Research Laboratories, Institute of Experimental Clinical Research, Aarhus University Hospital, Denmark. Bieke.Schrijvers@UGent.be
Bieke F
BF
Schrijvers
An S
AS
De Vriese
Johan
J
Van de Voorde
Ruth
R
Rasch
Norbert H
NH
Lameire
Allan
A
Flyvbjerg
D000419:Albuminuria; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D003404:Creatinine / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000503:physiopathology*; D004195:Disease Models, Animal; D005247:Feeding Behavior; D007668:Kidney / Q000033:anatomy & histology / Q000473:pathology / Q000503:physiopathology*; D008657:Metabolic Clearance Rate; D009929:Organ Size; D051381:Rats; D011922:Rats, Mutant Strains; D017208:Rats, Wistar
D001786:Blood Glucose; D003404:Creatinine