Endothelial dysfunction and diabetes: roles of hyperglycemia,impaired insulin signaling and obesity |
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Authors: | Wineke Bakker Etto C Eringa Pieter Sipkema Victor W M van Hinsbergh |
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Institution: | (1) Laboratory of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Van der Boechorststraat 7, 1081BT Amsterdam, The Netherlands |
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Abstract: | Endothelial dysfunction comprises a number of functional alterations in the vascular endothelium that are associated with
diabetes and cardiovascular disease, including changes in vasoregulation, enhanced generation of reactive oxygen intermediates,
inflammatory activation, and altered barrier function. Hyperglycemia is a characteristic feature of type 1 and type 2 diabetes
and plays a pivotal role in diabetes-associated microvascular complications. Although hyperglycemia also contributes to the
occurrence and progression of macrovascular disease (the major cause of death in type 2 diabetes), other factors such as dyslipidemia,
hyperinsulinemia, and adipose-tissue-derived factors play a more dominant role. A mutual interaction between these factors
and endothelial dysfunction occurs during the progression of the disease. We pay special attention to the possible involvement
of endoplasmic reticulum stress (ER stress) and the role of obesity and adipose-derived adipokines as contributors to endothelial
dysfunction in type 2 diabetes. The close interaction of adipocytes of perivascular adipose tissue with arteries and arterioles
facilitates the exposure of their endothelial cells to adipokines, particularly if inflammation activates the adipose tissue
and thus affects vasoregulation and capillary recruitment in skeletal muscle. Hence, an initial dysfunction of endothelial
cells underlies metabolic and vascular alterations that contribute to the development of type 2 diabetes.
E.C. Eringa is supported by the Dutch Diabetes Foundation (grant 2003.00.030), the Dutch Kidney foundation (grant C03.2046),
and the Dutch organization for scientific research (grant 916.76.179). V.W.M. van Hinsbergh is supported by the European Vascular
Genomics Network (grant LSHM-CT-2003–503254). |
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Keywords: | Endothelial dysfunction Diabetes Obesity Adipokines Hyperglycemia |
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