Insulin sensitivity is preserved despite disrupted endothelial function.
Insulin sensitivity is preserved despite disrupted endothelial function.
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尽管内皮功能受损，但胰岛素敏感性仍得以保留。
DOI：
10.1152/ajpendo.00006.2006
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Steinberg,HelmutO
中科院分区：
文献类型：
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作者：
Shankar,SudhaS;Considine,RobertV;Gorski,JChristopher;Steinberg,HelmutO
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 that1) endothelial dysfunction alone is insufficient to impair insulin-mediated glucose disposal, and2) 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.
