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Thromb Haemost 2009; 101(02): 345-350
DOI: 10.1160/TH08-07-0484
Endothelium and Vascular Biology
Schattauer GmbH

Prolonged exposure to high insulin impairs the endothelial PI3-kinase/Akt/nitric oxide signalling

Rosalinda Madonna
1   Institute of Cardiology, and Center of Excellence on Aging, “G. d’Annunzio” University, Chieti, Italy
,
Raffaele De Caterina
1   Institute of Cardiology, and Center of Excellence on Aging, “G. d’Annunzio” University, Chieti, Italy
2   CNR Institute of Clinical Physiology, Pisa, Italy
› Author AffiliationsFinancial support: This work has been supported through funding from the Center of Excellence on Aging (C.E.A.) Project, through a PRIN grant from the Italian Ministry of the University and Scientific Research, and through a grant from the Istituto Nazionale Ricerche Cardio -vascolari (I.N.R.C.), all to the Chair and Institute of Cardiology at “G. d’Annunzio” University, Chieti.
Further Information

Publication History

Received: 28 July 2008

Accepted after minor revision: 20 January 2008

Publication Date:
23 November 2017 (online)

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Summary

Hyperinsulinemia predicts future cardiovascular events, but may also contribute to atherosclerosis. We therefore studied the consequences of prolonged insulin treatment of human umbilical vein endothelial cells (HUVEC) on the phosphatidylinositol-3‘-kinase(PI3K)/Akt/nitric oxide(NO)-dependent insulin signaling, together with the expression of the pro-atherogenic molecule vascular cell adhesion molecule (VCAM)-1. HUVEC were incubated with insulin (10–11 to 10–7 M) in short- (30 min) and long-term (24 h to 3 days) incubations. In short-term incubations, insulin did not affect constitutive Akt and eNOS at any concentration, but significantly increased their active phosphorylated forms, and NO production. In long-term incubations, however, such insulin effects on the phosphorylated forms, as well as NO production, were attenuated, promoting an effect of insulin also at concentrations otherwise ineffective. Such effects were accompanied by a boosting of insulin effect on VCAM-1 surface expression. In contrast, under similar conditions, insulin did not exert any significant effect on the surface expression of ICAM-1 and E-selectin. Therefore, prolonged exposure of HUVEC to high insulin levels induces a downregulation of the PI3K/Akt/eNOS axis. Such impairment of insulin signalling in states of prolonged hyperinsulinemia pontially contributes to detrimental effects on atherogenesis in insulin resistance states, such as the metabolic syndrome and type 2 diabetes.

Keywords

Insulin - endothelial activation - vascular cell adhesion molecule-1 - type 2 diabetes - insulin resistance

 

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