Insulin sensitivity is preserved despite disrupted endothelial function
Open Access
- 1 October 2006
- journal article
- Published by American Physiological Society in American Journal of Physiology-Endocrinology and Metabolism
- Vol. 291 (4), E691-E696
- https://doi.org/10.1152/ajpendo.00006.2006
Abstract
It is well established that endothelial dysfunction and insulin resistance go hand in hand. However, it is unclear whether endothelial dysfunction per se is sufficient to impair insulin-mediated glucose uptake. We have previously reported that 4 wk of administration of the human immunodeficiency virus (HIV)-1 protease inhibitor indinavir to HIV-negative subjects induces endothelial dysfunction. Hence, we hypothesized that indinavir-induced endothelial dysfunction was associated with impaired insulin-mediated glucose disposal. We measured insulin-mediated glucose disposal at the level of the whole body, skeletal muscle, and vasculature by performing hyperinsulinemic euglycemic clamp, and vascular function studies, in a separate group of HIV-negative healthy nonobese subjects ( n = 13) before and after 4 wk of daily oral indinavir. Four weeks of indinavir resulted in a 113 ± 29% ( P < 0.01) reduction of endothelium-dependent vasodilation, consistent with our earlier findings. In addition, there was a significant impairment of insulin-mediated vasodilation (101 ± 14% before indinavir vs. 35 ± 15% after indinavir; P < 0.05). However, there was no significant change in insulin-mediated glucose disposal at the level of the whole body (8.9 ± 0.5 before indinavir vs. 8.5 ± 0.6 mg·kg−1·min−1after indinavir; P = 0.4), or skeletal muscle. Furthermore, in a separate group of four HIV-negative healthy nonobese subjects, we found that 4 wk of indinavir has no sustained effect on insulin-stimulated glucose uptake in adipose tissue. Thus our findings indicate that 1) endothelial dysfunction alone is insufficient to impair insulin-mediated glucose disposal, and 2) indinavir-induced endothelial dysfunction is likely due to a direct effect of the drug on the endothelium and is not coupled to the induction of insulin resistance.Keywords
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