Contribution of insulin resistance to vascular dysfunction

Abstract

Insulin is a vascular hormone, able to influence vascular cell responses. In this review, we consider the insulin actions on vascular endothelium and on vascular smooth muscle cells (VSMC) both in physiological conditions and in the presence of insulin resistance. In particular, we focus the relationships between activation of insulin signalling pathways of phosphatidylinositol-3 kinase (PI3-K) and mitogen-activated protein kinase (MAPK) and the different vascular actions of insulin, with a particular attention to the insulin ability to activate the pathway nitric oxide (NO)/cyclic GMP/PKG via PI3-K, owing to the peculiar relevance of NO in vascular biology. We also discuss the insulin actions mediated by the MAPK pathway (such as endothelin-1 synthesis and secretion and VSMC proliferation and migration) and by the interactions between the two pathways, both in insulin-sensitive and in insulin-resistant states. Finally, we consider the influence of free fatty acids, cytokines and endothelin on vascular insulin resistance.

Key words::

• Insulin
• insulin resistance
• endothelial cells
• vascular smooth muscle cells
• nitric oxide

Acknowledgements

This study was supported by a grant from Italian Ministero dell’Istruzione, Università e Ricerca (MIUR) COFIN 2004 within the project “The molecular basis of insulin resistance and their importance in the pathogenesis of the alterations of the vessel wall”, Local Coordinator: Giovanni Anfossi, National Coordinator: Amalia Bosia and by two grants from Regione Piemonte to Giovanni Anfossi (years 2004 and 2006) and to Mariella Trovati (years 2007 and 2008)

Declaration of interest: The authors report no conflict of interest.