Twenty-five years since the discovery of endothelium-derived relaxing factor (EDRF): Does a dysfunctional endothelium contribute to the development of type 2 diabetes?

Christopher Triggle, Andrew Howarth, Zhong Jian Cheng, Hong Ding

Research output: Contribution to journalReview article

20 Citations (Scopus)


Twenty-five years ago, the discovery of endothelium-derived relaxing factor opened a door that revealed a new and exciting role for the endothelium in the regulation of blood flow and led to the discovery that nitric oxide (NO) multi-tasked as a novel cell-signalling molecule. During the next 25 years, our understanding of both the importance of the endothelium as well as NO has greatly expanded. No longer simply a barrier between the blood and vascular smooth muscle, the endothelium is now recognized as a complex tissue with heterogeneous properties. The endothelium is the source of not only NO but also numerous vasoactive molecules and signalling pathways, some of which are still not fully characterized such as the putative endothelium-derived relaxing factor. Dysfunction of the endothelium is a key risk factor for the development of macro- and microvascular disease and, by coincidence, the discovery that NO was generated in the endothelium corresponds approximately in time with the increased incidence of type 2 diabetes. Primarily linked to dietary and lifestyle changes, we are now facing a global pandemic of type 2 diabetes. Characterized by insulin resistance and hyperglycaemia, type 2 diabetes is increasingly being diagnosed in adolescents as well as children. Is there a link between dietary-related hyperglycaemic insults to the endothelium, blood flow changes, and the development of insulin resistance? This review explores the evidence for and against this hypothesis.

Original languageEnglish
Pages (from-to)681-700
Number of pages20
JournalCanadian Journal of Physiology and Pharmacology
Issue number8-9
Publication statusPublished - Aug 2005
Externally publishedYes



  • Diabetes
  • Endothelium
  • Hyperglycaemia
  • Insulin
  • Nitric oxide
  • Oxidative stress

ASJC Scopus subject areas

  • Physiology
  • Pharmacology

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