Cardiovascular Toxicology

, Volume 8, Issue 1, pp 15–22

Severe Impairment of Endothelial Function with the HIV-1 Protease Inhibitor Indinavir is not Mediated by Insulin Resistance in Healthy Subjects

  • Michael P. Dubé
  • Jude Christopher Gorski
  • Changyu Shen

DOI: 10.1007/s12012-007-9010-y

Cite this article as:
Dubé, M.P., Gorski, J.C. & Shen, C. Cardiovasc Toxicol (2008) 8: 15. doi:10.1007/s12012-007-9010-y


Endothelial dysfunction may contribute to increased cardiovascular events among HIV-1-infected patients receiving antiretroviral therapy. The HIV-1 protease inhibitor indinavir causes both vascular dysfunction and insulin resistance, but the relationship between the two disturbances is not established. Endothelium-dependent vasodilation (EDV), insulin-mediated vasodilation (IMV), and whole body and leg glucose uptake during a euglycemic hyperinsulinemic clamp (40 mU/m2/min) were measured before and after four weeks of indinavir in nine healthy men. EDV fell from 270 ± 67% above basal to 124 ± 30% (P = 0.04) and IMV from 56 ± 14% above basal to 8 ± 8% (P = 0.001) with indinavir. During the clamp, arteriovenous glucose difference and leg glucose uptake were not significantly different after indinavir and whole-body glucose uptake was only modestly reduced (8.0 ± 0.8 vs. 7.2 ± 0.8 mg/kg/min, P = 0.04). The change in EDV did not correlate with the change in whole-body glucose uptake after indinavir (r = 0.21, P = 0.6). Despite marked impairment of endothelial function and IMV with indinavir, only modest, inconsistent reductions in measures of insulin-stimulated glucose uptake occurred. This suggests that indinavir’s effects on glucose metabolism are not directly related to indinavir-associated endothelial dysfunction. Studies of the vascular effects of newer protease inhibitors are needed.


Endothelial dysfunctionInsulin sensitivityIndinavirHIV-1 protease inhibitors



Endothelium-dependent vasodilation


Insulin-mediated vasodilation


Nitric oxide




Arterio-venous glucose difference

Copyright information

© Humana Press Inc. 2007

Authors and Affiliations

  • Michael P. Dubé
    • 1
  • Jude Christopher Gorski
    • 2
    • 3
  • Changyu Shen
    • 4
  1. 1.Department of Medicine and the Division of Infectious DiseasesIndiana University School of Medicine, Wishard Memorial HospitalIndianapolisUSA
  2. 2.Division of Clinical PharmacologyIndiana University School of MedicineIndianapolisUSA
  3. 3.Mylan Pharmaceuticals, Inc.MorgantownUSA
  4. 4.Division of BiostatisticsIndiana University School of MedicineIndianapolisUSA