Relevance of the Vascular Effects of Insulin in the Rationale of its Therapeutical Use

Authors: Anfossi, Giovanni; Russo, Isabella; Doronzo, Gabriella; Trovati, Mariella

Source: Cardiovascular & Haematological Disorders - Drug Targets(Formerly Current Drug Targets - Cardiovascular & Hematological Disorders), Volume 7, Number 4, December 2007 , pp. 228-249(22)

Publisher: Bentham Science Publishers

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Abstract:

Beyond carbohydrate, lipid and protein metabolism, insulin influences hemostasis, vascular tone and angiogenesis. Insulin per se causes a slow-acting vasodilation selectively occurring in skeletal muscle tissue, mainly related to an endothelium-dependent mechanism. Insulin-induced vasodilation is attenuated by the secretion of endothelin-1 and by the stimulation of sympathetic activity. The direct vasodilating effect of insulin is deeply reduced in the insulin-resistant states. The insulin effects on platelet aggregation and inflammatory response are attributable to increased synthesis of nitric oxide, and are deeply reduced in the insulin-resistant states. Furthermore, insulin reduces oxidative stress and promotes angiogenesis and proliferation of vascular smooth muscle cells. The involvement of insulin signalling pathways in these different insulin actions both in insulin sensitive and in insulin resistant states and the concept of “selective insulin resistance” are discussed.

The vascular effects of insulin are generally ignored in the clinical practice, despite the evidences that insulin infusion with algorithms aiming to provide an optimal blood glucose control improves the clinical outcomes of patients with severe acute illness and myocardial infarction. Aim of this review is to clarify whether the vascular effects of insulin could represent a new “rationale” for its therapeutical use, independently of the well known metabolic actions.

Keywords: Endothelial cells; endothelin-1; insulin; insulin resistance; platelets; vascular smooth muscle cells

Document Type: Research article

DOI: http://dx.doi.org/10.2174/187152907782793581

Publication date: 2007-12-01

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Cardiovascular & Hematological Disorders - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in cardiovascular and hematological disorders e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will contain a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in cardiovascular and hematological disorders. As the discovery, identification, characterization and validation of novel human drug targets for cardiovascular and hematological drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.

Relevance of the Vascular Effects of Insulin in the Rationale of its Therapeutical Use

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