Role of oxidative stress in diabetes-mediated vascular dysfunction: Unifying hypothesis of diabetes revisited

Stephen W. Schaffer, Chian Ju Jong, Mahmood S Mozaffari

Research output: Contribution to journalReview article

73 Citations (Scopus)

Abstract

Oxidative stress is recognized as a key participant in the development of diabetic complications in the vasculature. One of the seminal studies advancing the role of oxidative stress in vascular endothelial cells proposed that oxidative stress-mediated diversion of glycolytic intermediates into pathological pathways was a key underlying element in the development of diabetic complications. It is widely recognized that flux through glycolysis slows during diabetes. However, several bottlenecks develop in the glycolytic pathway, including glucose transport, phosphofructokinase, glyceraldehyde-3-phosphate dehydrogenase and pyruvate kinase. Of these limiting steps in glycolysis, glyceraldehyde-3-phosphate dehydrogenase is most sensitive to oxidative stress, leading to the hypothesis that glyceraldehyde-3-phosphate inactivation by ribosylation underlies the diversion of glycolytic intermediates into pathological pathways. However, recent studies question the mechanism underlying the effect of reactive oxygen species on key enzymes of the glycolytic pathway. The present review critiques the major premises of the hypothesis and concludes that further study of the role of oxidative stress in the development of diabetes-mediated vasculature dysfunction is warranted.

Original languageEnglish (US)
Pages (from-to)139-149
Number of pages11
JournalVascular Pharmacology
Volume57
Issue number5-6
DOIs
StatePublished - Nov 1 2012

Fingerprint

Blood Vessels
Oxidative Stress
Glyceraldehyde-3-Phosphate Dehydrogenases
Glycolysis
Diabetes Complications
Glyceraldehyde 3-Phosphate
Phosphofructokinases
Pyruvate Kinase
Reactive Oxygen Species
Endothelial Cells
Glucose
Enzymes

Keywords

  • Diabetic complications
  • Glyceraldehyde-3-phosphate dehydrogenase inactivation by ribosylation
  • Oxidative stress
  • Vascular damage

ASJC Scopus subject areas

  • Physiology
  • Molecular Medicine
  • Pharmacology

Cite this

Role of oxidative stress in diabetes-mediated vascular dysfunction : Unifying hypothesis of diabetes revisited. / Schaffer, Stephen W.; Jong, Chian Ju; Mozaffari, Mahmood S.

In: Vascular Pharmacology, Vol. 57, No. 5-6, 01.11.2012, p. 139-149.

Research output: Contribution to journalReview article

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