Impact of mitochondrial ROS production on diabetic vascular complications

Diabetes Res Clin Pract. 2007 Sep;77 Suppl 1:S41-5. doi: 10.1016/j.diabres.2007.01.031. Epub 2007 Apr 23.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Citric Acid Cycle
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / metabolism
  • Diabetic Angiopathies / physiopathology*
  • Humans
  • Mitochondria / physiology*
  • Models, Biological
  • Reactive Oxygen Species / metabolism*


  • Reactive Oxygen Species
  • 8-Hydroxy-2'-Deoxyguanosine
  • Deoxyguanosine