Augmented NADPH oxidase activity and p22phox expression in monocytes underlie oxidative stress of patients with type 2 diabetes mellitus.
BACKGROUND
This study was to test the hypothesis that enhanced oxidative stress is induced in monocytes with over-activated NADPH oxidase during the development of type 2 diabetes mellitus.


METHODS
Levels of glucose and lipids were analyzed in 73 diabetic patients and 36 controls. Superoxide dismutase (SOD), malondialdehyde (MDA), reactive oxygen species (ROS) and protein carbonylation were tested. Expression of NADPH oxidase was examined and p47phox translocation was assessed.


RESULTS
With the abnormality of glucose and lipid metabolism, diabetic patients showed a higher oxidative stress state indicated by decreased SOD activity but elevated MDA and protein carbonylation level. Monocytes in diabetes also showed elevated ROS generation and protein carbonylation level. Furthermore, NADPH oxidase was highly activated in monocytes represented by p22phox up-regulation and p47phox translocation. Significant positive bivariate correlation was found between glucose and MDA level as well as p22phox expression. In vitro experiments also indicated that glucose could stimulate ROS generation in a NADPH oxidase dependent manner. Moreover, we carried out same measurement in 40 diabetic patients with anti-diabetic intervention and obtained the reinforced results.


CONCLUSIONS
Hyperglycemia is the main factor which induces oxidative stress mainly by activation of NADPH oxidase in monocytes of diabetic patients.
Beijing Institute of Geriatrics, Ministry of Health, Beijing, People's Republic of China.
Xiuqing
X
Huang
Mingxiao
M
Sun
Dongxiao
D
Li
Jin
J
Liu
Hanbang
H
Guo
Yuan
Y
Dong
Lei
L
Jiang
Qi
Q
Pan
Yong
Y
Man
Shu
S
Wang
Jian
J
Li
D000328:Adult; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia; D008315:Malondialdehyde; D008875:Middle Aged; D009000:Monocytes / Q000201:enzymology / Q000378:metabolism*; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D050050:Protein Carbonylation; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D015854:Up-Regulation / Q000235:genetics
D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; C086986:CYBA protein, human