Authors: Tesauro, Manfredi; Iantorno, Micaela; Schinzari, Francesca; Cardillo, Carmine

Source: Current Hypertension Reviews, Volume 5, Number 4, November 2009 , pp. 251-261(11)

Publisher: Bentham Science Publishers

Abstract:

Over the last ten years it has become clear that vascular actions of insulin extend beyond its ability to increase skeletal muscle blood flow and glucose uptake. In addition to its role in regulating glucose, protein, and fatty acid metabolism insulin exhibits distinct effects on the vascular system.

In this review we will clarify the influence exerted by insulin in the maintenance of endothelial function and the relationship between insulin resistance, endothelial dysfunction and hypertension. The mechanisms by which insulin resistance leads to endothelial dysfunction are multiple and complex. Most of the abnormalities present in the insulin resistance syndrome (obesity, hyperglicemia, hypertension, dyslipidemia) are linked to endothelial dysfunction. Insulin vasodilates skeletal muscle vasculature through release of nitric oxide (NO), a mechanism that accounts for 30% of insulin overall action to stimulate glucose uptake. On the one hand, PI3-kinase-dependent insulin signalling pathways in endothelium related to production of NO share striking similarities with metabolic pathways in skeletal muscle that promote glucose uptake. On the other hand, distinct non-metabolic insulin signaling pathways (MAPK-dependent insulin signalling pathways) regulate secretion of the vasoconstrictor endothelin-1 (ET-1) from endothelium. Insulin resistance is characterized by the specific impairment of PI 3-kinase-dependent signalling that causes imbalance between NO and ET-1 production, leading to reduction of blood flow that, in turn, worsens insulin resistance. Insulin resistance is the common metabolic defect underlying type 2 diabetes, hypertension, obesity, dyslipidemia and coronary heart diseases; therefore, improving insulin sensitivity may provide an opportunity for simultaneous therapeutic strategies on metabolic and cardiovascular diseases.

Document Type: Research article

DOI: http://dx.doi.org/10.2174/157340209789587744

Publication date: 2009-11-01

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• Current Hypertension Reviews publishes frontier reviews on all the latest advances on hypertension and its related areas e.g. nephrology, clinical care, and therapy. The journal's aim is to publish the highest quality review articles dedicated to clinical research in the field. The journal is essential reading for all clinicians and researchers in the field of hypertension.