Diabetic vascular dysfunction

Links to glucose-induced reductive stress and VEGF

Ronald Tilton

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

A complete biochemical understanding of the mechanisms by which hyperglycemia causes vascular functional and structural changes associated with the diabetic milieu still eludes us. In recent years, the numerous biochemical and metabolic pathways postulated to have a causal role in the pathogenesis of diabetic vascular disease have been distilled into several unifying hypotheses. These involve either increased reductive or oxidative stress to the cell, or the activation of numerous protein kinase pathways, particularly protein kinase C and mitogen-activated protein kinases. As detailed below, there is tremendous crosstalk between these competing hypotheses. We propose that increased tissue glucose levels alter cytosolic coenzyme balance by increased flux of glucose through the sorbitol pathway increasing free cytosolic NADH levels. Increased NADH levels can generate reactive oxygen species via numerous mechanisms, lead to the formation of intracellular advanced glycation end products, and induce growth factor expression via mechanisms involving protein kinase C activation. The elevation in growth factors, particularly vascular endothelial growth factor (VEGF), is responsible for the vascular dysfunction via numerous mechanisms reported here in detail.

Original languageEnglish (US)
Pages (from-to)390-407
Number of pages18
JournalMicroscopy Research and Technique
Volume57
Issue number5
DOIs
StatePublished - Jun 1 2002
Externally publishedYes

Fingerprint

vascular endothelial growth factors
NAD (coenzyme)
protein kinase C
blood vessels
glucose
NAD
Protein Kinase C
growth factors
Vascular Endothelial Growth Factor A
Blood Vessels
Glucose
biochemical pathways
Intercellular Signaling Peptides and Proteins
proteins
Proteins
Diabetic Angiopathies
vascular diseases
Advanced Glycosylation End Products
biochemical mechanisms
coenzymes

Keywords

  • Advanced glycation endproducts
  • Diabetes
  • Growth factors
  • Hyperglycemia pseudohypoxia
  • Mitogen-activated protein kinases
  • Protein kinase C
  • Reactive oxygen species
  • Sorbitol pathway
  • Vascular permeability
  • VEGF

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Anatomy
  • Instrumentation

Cite this

Diabetic vascular dysfunction : Links to glucose-induced reductive stress and VEGF. / Tilton, Ronald.

In: Microscopy Research and Technique, Vol. 57, No. 5, 01.06.2002, p. 390-407.

Research output: Contribution to journalArticle

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