Oxidative and nitrosative stress and progression of diabetic nephropathy in type 2 diabetes.
BACKGROUND
The role of nitric oxide (NO) is controversial in diabetes nephropathy progression and the mechanisms remain unknown, especially in non-obese type 2 diabetes. To examine mechanisms of nephropathy progression in non-obese type 2 diabetes, we used spontaneously diabetic Torii (SDT) rats, a newly established model of non-obese type 2 diabetes.


METHODS
Fourteen male Sprague-Dawley rats were used as a control (20 weeks, n = 6; 30 weeks, n = 8), and 20-week-old male SDT rats were divided into 2 groups: diabetic (DM, n = 8) and DM + insulin (n = 8) groups. Twenty- and 36-week-old rats were sacrificed, and blood, urine, and histomorphometric analyses, mRNA expression analysis of endothelial NO synthase (eNOS) and NADPH oxidase, and blood pressure measurement were performed.


RESULTS
At 36 weeks, NO metabolites, and 8-hydroxydeoxyguanosine (8-OHdG) were significantly higher in the diabetic group than in the other 2 groups. Further renal studies showed increased glomerular volume and mesangial area, and intensified eNOS, 8-OHdG, and nitrotyrosine immunostaining in the diabetic group. Oxidative and nitrosative stress were positively associated with increased glomerular volume and mesangial area, which were mostly recovered by insulin therapy.


CONCLUSIONS
NO and oxidative stress increased in SDT rats, suggesting that these play key roles in nephropathy progression in non-obese type 2 diabetes.
Division of Nephrology and Kidney Center, Kobe University School of Medicine, Japan.
Hideki
H
Fujii
Keiji
K
Kono
Kentaro
K
Nakai
Shunsuke
S
Goto
Hirotaka
H
Komaba
Yasuhiro
Y
Hamada
Masami
M
Shinohara
Riko
R
Kitazawa
Sohei
S
Kitazawa
Masafumi
M
Fukagawa
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000378:metabolism*; D018450:Disease Progression; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley
D009569:Nitric Oxide