Resistance to glomerular injury in the diabetic biobreeding rat.
This study was designed to determine whether the diabetic BioBreeding rat develops significant renal injury following long-term moderate to severe hyperglycaemia. Diabetic and control rats were followed from the onset of diabetes (2-4 months) to 18 months of age. Frank proteinuria and/or albuminuria were always absent. Glomerular filtration rate, measured by inulin clearance (ml min-1 (100 g body weight)-1), was significantly higher in diabetic rats than in controls at 10, 12 and 18 months of age. Advanced glycosylation end-product cross-links assessed by percentage solubility of tail tendon collagen were moderately increased in diabetic compared with control animals. Urinary excretion of advanced glycosylation end-products in unfractionated urine and in urine fractionated for low molecular mass peptides (< 10 kDa) was 11-fold greater in the diabetic rats than in the control group. Urinary excretion of nitric oxide metabolites (nmol NO2- and NO3- (24 h)-1) were significantly (P < 0.05) greater in diabetic rats than in controls after 8 months of age. Mild histopathology resembling human diabetic nephropathy, including increased mesangial volume and glomerular basement membrane thickness, was detected at 18 months of age. The findings of hyperfiltration and mild glomerular morphological changes in diabetic BioBreeding rats are similar to the abnormalities seen in stage 2 human diabetic nephropathy. We hypothesize that two factors which may contribute to the resistance or tolerance to renal injury in the BioBreeding diabetic rat are increased nitric oxide production and the decreased accumulation of advanced glycosylation end-products.
Feld
L G
LG
Department of Pathology, State University of New York at Buffalo, USA.
Cachero
S
S
Ellis
E N
EN
Dedeoglu
O
O
Ueda
Y
Y
Leonard
C
C
Letizia
R
R
Mallon
V
V
Van Liew
J B
JB
D000818:Animals; D003920:Diabetes Mellitus / Q000473:pathology* / Q000503:physiopathology* / Q000652:urine; D017127:Glycation End Products, Advanced / Q000378:metabolism; D007668:Kidney / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000473:pathology*; D008297:Male; D051381:Rats; D011913:Rats, Inbred BB / Q000502:physiology*; D013997:Time Factors
D017127:Glycation End Products, Advanced