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KMID : 0356620060210060448
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Journal of Korean Society of Endocrinology
2006 Volume.21 No. 6 p.448 ~ p.459
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Mechanism of Developing Diabetic Vascular Complication by Oxidative Stress
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김보현
손석만
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Abstract
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Macrovascular and microvascular diseases are currently the principal causes of morbidity and mortality in the patients with diabetes mellitus. Oxidative stress has been postulated to be a major contributor to the pathogenesis of these events. There is considerable evidence that many biochemical pathways that are adversely affected by hyperglycemia are associated with the generation of reactive oxygen species, and this ultimately leads to increased oxidative stress in a variety of tissues. In the absence of appropriate compensation by the endogenous antioxidant defense network, increased oxidative stress leads to the activation of stress-sensitive intracellular signaling pathways and the formation of gene products that cause cellular damage and contribute to the late complications of diabetes. Hyperglycemia increases oxidant production by multiple pathways rather than by a single dominant pathway. Glucose can undergo nonenzymatic reactions to form gluco-oxidants and glycated products, which can be oxidants. Metabolism of excessive intracellular glucose can occur by several processes such as aldose reductase, mitochondrial oxidative phosphorylation, activation of NAD(P)H oxidases, and the alteration of the NADPH/NADP ratios. Reactive oxygen species participate in vascular smooth muscle cell growth and migration, modulation of endothelial function, including abnormal endothelium-dependent relaxation and the expression of a proinflammatory phenotype, and modification of the extracellular matrix. All of these events contribute to the development of diabetic microvascular and macrovascular complications, suggesting that the sources of reactive oxygen species and the signaling pathways that they modify may represent important therapeutic targets.
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KEYWORD
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Diabetic complication, Diabetes, NADPH/NADP, Oxidative stress
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