title: Pathophysiological mechanisms of diabetic angiopathy.
abstract: The sequelae of chronic hyperglycemia in diabetes of all phenotypes are divided into microvascular and macrovascular complications. Microvascular disease causes blindness, renal failure, and neuropathy, and diabetes-accelerated macrovascular disease causes excessive risk for myocardial infarction, stroke, and lower limb amputation. The link between chronic hyperglycemia and vascular damage has been established by four independent biochemical abnormalities: increased polyol pathway flux, increased formation of advanced glycation end-products (AGEs), activation of protein kinase C (PKC), and increased hexosamine pathway flux. These seemingly unrelated pathways have an underlying common denominator: overproduction of superoxide by the mitochondrial electron transport chain. Mitochondrial reactive oxygen species (ROS) partially inhibit the glycolytic enzymes glyceraldehyde-3-phosphate dehydrogenase, which diverts increased substrate flux from glycolysis to pathways of glucose overutilization. Preliminary experimental evidence in vivo suggests that this new paradigm provides a novel basis for research and drug development.
authors.affiliation: 5th Medical Department, University Hospital Mannheim, Faculty of Clinical Medicine Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany. hans-peter.hammes@med5.uni-heidelberg.de
authors.forename: Hans Peter
authors.initials: HP
authors.lastname: Hammes
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003925:Diabetic Angiopathies / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006801:Humans; D006943:Hyperglycemia / Q000150:complications; D008928:Mitochondria / Q000502:physiology; D013481:Superoxides / Q000009:adverse effects; D014652:Vascular Diseases / Q000209:etiology*
chemical_list: D013481:Superoxides