Endothelial cell dysfunction in type I and II diabetes

The cellular basis for dysfunction

Malarvannan Pannirselvam, Todd J. Anderson, Christopher Triggle

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Micro- and macrovascular complications are the leading causes of mortality in Types I and II diabetes. Hyperglycemia results in increased advanced glycosylation end (AGE) products, oxidative stress, increased sorbitol levels, and increased activation of protein kinase C. These effects of hyperglycemia eventually lead to impaired endothelium-dependent relaxation to vasoactive substances such as acetylcholine and bradykinin. Increased oxidative stress, which will reduce levels of nitric oxide (NO), and/or decreased bioavailability of tetrahydrobiopterin (BH4), a cofactor for endothelial NO synthase (eNOS), may lead to a phenomenon called "uncoupling" of eNOS and this leads to endothelial dysfunction. Uncoupled NOS produces superoxide anions which lead to a further reduction in NO bioavailability. Thus, restoring BH4 levels and antioxidant activity could prove to be novel approaches for the treatment of endothelial dysfunction in Type I and II diabetes.

Original languageEnglish
Pages (from-to)28-41
Number of pages14
JournalDrug Development Research
Volume58
Issue number1
DOIs
Publication statusPublished - 1 Jan 2003
Externally publishedYes

Fingerprint

Oxidative stress
Endothelial cells
Medical problems
Type 1 Diabetes Mellitus
Hyperglycemia
Type 2 Diabetes Mellitus
Biological Availability
Nitric Oxide
Oxidative Stress
Endothelial Cells
Advanced Glycosylation End Products
Sorbitol
Nitric Oxide Synthase Type III
Bradykinin
Nitric Oxide Synthase
Superoxides
Protein Kinase C
Acetylcholine
Endothelium
Antioxidants

Keywords

  • "uncoupled" NOS
  • Endothelial dysfunction
  • Oxidative stress
  • Tetrahydrobiopterin
  • Type I diabetes
  • Type II diabetes

ASJC Scopus subject areas

  • Organic Chemistry
  • Drug Discovery
  • Pharmacology

Cite this

Endothelial cell dysfunction in type I and II diabetes : The cellular basis for dysfunction. / Pannirselvam, Malarvannan; Anderson, Todd J.; Triggle, Christopher.

In: Drug Development Research, Vol. 58, No. 1, 01.01.2003, p. 28-41.

Research output: Contribution to journalArticle

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