Treatments in Endocrinology

, Volume 2, Issue 5, pp 293–304

Mechanisms Underlying Endothelial Dysfunction in Diabetes Mellitus

Therapeutic Implications
  • Ulrich Hink
  • Nikos Tsilimingas
  • Maria Wendt
  • Thomas Münzel
Current Opinion


Hyperglycemia is the major causal factor in the development of endothelial dysfunction in patients with diabetes mellitus. Although the mechanisms underlying this phenomenon are likely to be multifactorial, recent in vivo and in vitro studies have indicated a crucial role of the diacylglycerol (DAG)-protein kinase C (PKC) pathway in mediating this phenomenon. PKC may have multiple adverse effects on vascular function, including the activation of superoxide-producing enzymes such as the nicotinamide adenine dinicleotide phosphate (NADPH) oxidase as well as increased expression of a dysfunctional, superoxide-producing, uncoupled endothelial nitric oxide synthase (NOS III).

PKC-mediated Superoxide production may inactivate nitric oxide (NO) derived from endothelial NOS III, but also may inhibit the activity and/or expression of the NO downstream target, the soluble guanylyl cyclase. Among the different isoforms of PKC, mainly the β-isoforms have been shown to be activated.

Recent studies with selective (isoform-specific) and non-selective PKC inhibitors show that they are able to beneficially influence glucose-induced endothelial dysfunction in experimental animal models as well as in patients, pointing to the therapeutic potential of these compounds in the prevention and treatment of vascular complications of diabetes.


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Copyright information

© Adis Data Information BV 2003

Authors and Affiliations

  • Ulrich Hink
    • 1
  • Nikos Tsilimingas
    • 1
  • Maria Wendt
    • 1
  • Thomas Münzel
    • 1
  1. 1.Division of CardiologyUniversity Hospital EppendorfHamburgGermany
  2. 2.Universitätsklinikum Hamburg-Eppendorf, Abteilung für KardiologieHamburgGermany

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