title: Molecular and clinical aspects of endothelial dysfunction in diabetes.
abstract: Diabetic patients have an increased risk for cardiovascular complications with respect to the general population. Micro- and macrovascular complications such as nephropathy, retinopathy, atherosclerosis, and coronary artery disease are usually preceded by endothelial dysfunction, a condition characterized by impaired vasorelaxation resulting from reduced bioavailability of the endothelial mediator nitric oxide (NO). Nitric oxide is among endothelial mediators released by endothelial cells in response to insulin stimulation. Therefore, metabolic abnormalities such as insulin resistance, dyslipidemia, compensatory hyperinsulinemia and overt hyperglycemia may all contribute to impaired NO bioavailability and abnormal vasodilatation in diabetic patients. Each of these alterations may trigger endothelial dysfunction by multiple intracellular mechanisms including accelerated formation of advanced glycolysis end products, activation of protein kinase C, increased pro-inflammatory signaling, and impaired sensitivity of the PI 3-kinase signaling pathways. This review outlines the most important mechanisms by which insulin takes part in physiological regulation of endothelial function. Abnormal insulin signaling in endothelium under diabetic conditions and patho-physiological consequences on cardiovascular homeostasis will also be discussed.
authors.affiliation: Department of Pharmacology and Human Physiology, Medical School, University of Bari, Policlinico-Piazza G. Cesare 11, Bari, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Nacci
authors.forename: Mariela
authors.initials: M
authors.lastname: Tarquinio
authors.forename: Monica
authors.initials: M
authors.lastname: Montagnani
mesh_terms: D048909:Diabetes Complications / Q000503:physiopathology*; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology*; D004730:Endothelium, Vascular / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism
chemical_list: D007328:Insulin; D009569:Nitric Oxide