Diabetes and Endothelial Dysfunction

  • Tatsuya MaruhashiEmail author
  • Yasuki Kihara
  • Yukihito HigashiEmail author


In patients with diabetes mellitus, endothelial dysfunction is the initial step in the process of atherosclerosis and plays an important role in the development of this condition, leading to diabetic vascular complications. Oxidative stress induced by hyperglycemia and acute glucose fluctuations are associated with endothelial dysfunction through inactivating nitric oxide (NO) by excess production of reactive oxygen species (ROS). Under the condition of insulin resistance, NO production is selectively impaired, whereas endothelin-1 (ET-1) secretion is preferentially activated in endothelial cells, leading to endothelial dysfunction in obese or overweight diabetic patients. On the other hand, endothelial dysfunction might contribute to insulin resistance in skeletal muscle. Reduced NO production through oxidative stress and selective insulin resistance in endothelial cells contributes to decreased glucose uptake by skeletal muscle due to a delayed increase in insulin concentration in the interstitium of the skeletal muscle. Therefore, insulin resistance is further exacerbated through a vicious cycle of endothelial dysfunction and reduced glucose uptake by skeletal muscle. From a clinical perspective, it is important to select an appropriate intervention that is effective in improving endothelial dysfunction for treatment of patients with diabetes mellitus.

In addition to lifestyle modifications, antidiabetic agents that improve insulin sensitivity are anticipated to improve endothelial function and prevent cardiovascular events in patients with diabetes mellitus.


Endothelial function Diabetes mellitus Oxidative stress Insulin resistance 


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Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Department of Cardiovascular Medicine, Graduate School of Biomedical and Health SciencesHiroshima UniversityHiroshimaJapan
  2. 2.Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and MedicineHiroshima UniversityHiroshimaJapan
  3. 3.Division of Regeneration and Medicine, Medical Center for Translational and Clinical ResearchHiroshima University HospitalHiroshimaJapan

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