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Diabetes Res Clin Pract. 2007 Sep;77 Suppl 1:S41-5. Epub 2007 Apr 23.

Impact of mitochondrial ROS production on diabetic vascular complications.

Author information

1
Department of Metabolic Medicine, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan. takeshi@kaiju.medic.kumamoto-u.ac.jp

Abstract

Vascular complications are the leading cause of morbidity and mortality in patients with diabetes. Four main molecular mechanisms have been implicated in glucose-mediated vascular disease. There are: glucose-induced activation of protein kinase C (PKC) isoforms; increased formation of glucose-derived advanced glycation end-products (AGE); increased glucose flux through the aldose reductase pathway; and increased production of reactive oxygen species (ROS). Here we demonstrate that hyperglycemia-induced production of ROS is abrogated by inhibitors of mitochondrial metabolism, or by overexpression of uncoupling protein-1 or manganese superoxide dismutase. Normalization of mitochondrial ROS production by each of these agents prevents glucose-induced activation of PKC, formation of AGE, and accumulation of sorbitol in bovine vascular endothelial cells. We also claim that 8-hydroxydeoxyguanosine, which represents mitochondrial oxidative damage was elevated in patients with either retinopathy, albuminuria or increased intima-media thickness of carotid arteries. These results suggest that hyperglycemia induces mitochondrial ROS production, and which can associate to the pathogenesis of diabetic vascular complications.

PMID:
17452060
DOI:
10.1016/j.diabres.2007.01.031
[Indexed for MEDLINE]

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