LETTER TO THE EDITOR
Vascular effect of insulin in endothelial dysfunction
Wolfram Doehner, MDa,
Ian F. Godsland, PhDa and
Stefan D. Anker, MD, PhDa
a National Heart and Lung Institute, Imperial College School of Medicine, Clinical Cardiology, Royal Brompton Hospital, Dovehouse Street, London SW3 6LY, United Kingdom
We read with interest the article by Hirashima et al. (1) in a recent issue of the Journal. The investigators report on the effect of vitamin C on endothelial function and insulin sensitivity in patients with coronary spastic angina, and they present further evidence that endothelial function might be one of the factors regulating insulin sensitivity. We would like to add some comments about the insulin-endothelium interplay.
Hirashima et al. (1) argue that endothelium mediates insulin resistance merely indirectly, via impaired vasodilator capacity, leading to a reduced supply of both insulin and glucose to the glucose utilizing tissues such as skeletal muscle. It might also be added that endothelium itself is an insulin-sensitive tissue, and the direct vasodilator effect of insulin-stimulating endothelial nitric oxide release (2,3) may further amplify the glucose utilization of the peripheral tissue.
Accordingly, under conditions of endothelial dysfunction a reduced vasodilator effect of insulin has been reported (4). We were surprised, however, that Hirashima et al. (1) report no changes in hemodynamics in both controls and patients during the insulin-sensitivity test. This finding has not been discussed by the researchers. From the amount of insulin and glucose administered according to the protocol, one would have expected to see a vasodilator effect, particularly in control subjects. A difference between the control group and patients with impaired endothelial function would seem plausible. Moreover, a recovery of insulin-mediated vasodilation through improvement of the cellular redox state (such as vitamin C supplementation) would strongly support the current opinion of insulin’s direct effect on endothelial function regulating vascular tone.
We have previously shown that in healthy control subjects, but not in patients with coronary artery disease, forearm blood flow increases after an intravenous administration of glucose (5). The amount of glucose administered in our study (0.5 g/kg) was similar to the amount of glucose administered by Hirashima et al. (1). Although we gave glucose as a bolus, a vasodilator effect on forearm blood flow for up to 180 min was recorded.
One explanation for the different finding in this study could be the method employed for assessment of insulin sensitivity. By suppressing endogenous insulin response to a glucose stimulus with sandostatin, the closed feedback loop by which glucose and insulin concentrations mutually modify one another is interrupted. It is uncertain whether the blockade of endogenous insulin secretion or the unphysiologic steady state may also affect other insulin-related pathways, such as the insulin-mediated augmentation of endothelium-dependent vasodilation.
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References
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- Hirashima O, Kawano H, Motoyama T, et al. Improvement of endothelial function and insulin sensitivity with vitamin C in patients with coronary spastic angina: possible role of reactive oxygen species. J Am Coll Cardiol. 2000;35:1860–1866[Abstract/Free Full Text]
- Steinberg HO, Brechtel G, Johnson A, Fineberg N, Baron AD. Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release. J Clin Invest. 1994;94:1172–1179[Medline]
- Scherrer U, Randin D, Vollenweider P, Vollenweider L, Nicod P. Nitric oxide release accounts for insulin’s vascular effects in humans. J Clin Invest. 1994;94:2511–2515[Medline]
- Steinberg HO, Chaker H, Leaming R, Johnson A, Brechtel G, Baron AD. Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance. J Clin Invest. 1996;97:2601–2610[Medline]
- Leyva F, Rauchhaus M, Anker SD, et al. Non-invasive assessment of vascular function; paradoxical vascular response to intravenous glucose in coronary heart disease. Eur Heart J. 2000;21:39–44[Abstract/Free Full Text]
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