Endocrine Abstracts (2001) 2 SP8

ROLE OF INSULIN IN REGULATION OF VASCULAR ENDOTHELIAL FUNCTION

JMC Connell


Dept Medicine & Therapeutics, University of Glasgow.


Insulin resistance is associated with a variety of cardiovascular disorders, including hypertension, non-insulin dependent diabetes mellitus, coronary artery disease and polycystic ovary syndrome. The mechanism of reduced insulin-stimulated glucose uptake in these conditions is unclear, but is likely to involve defects in cellular components of insulin signalling. All of the disorders above are characterised by abnormal vascular endothelial function, with reduced availability of nitric oxide and it is now apparent that endothelial dysfunction is a common association with insulin resistance. In previous studies we have shown that insulin resistance does, indeed, correlate with reduced nitric oxide availability in healthy volunteers and in patients with hypertension and diabetes. Insulin is a directly acting arterial vasodilator, and this is a nitric oxide dependent effect. There is a positive association between insulin-mediated vasodilatation and nitric oxide-dependent vasodilatation. Furthermore, we have recently shown that this relationship is also present in subjects with polycystic ovary syndrome, in whom there is a defect in insulin relaxation of resistance arteries. Thus, in all circumstances studied there is a parallel relationship between the metabolic and vascular actions of insulin.

The mechanism through which insulin acts to regulate vascular endothelial nitric oxide production remains to be elucidated. We have recently shown that all components of the insulin-signalling pathway are present in cultured human aortic endothelial cells, and that insulin increases nitric oxide production by these cells. It is tempting, therefore, to speculate that cardiovascular disorders are characterised by a common primary defect in the insulin signalling pathway that results in reduced insulin-stimulated glucose uptake in adipose and skeletal muscle tissue and in reduced nitric oxide production in the endothelium.

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