Indinavir acutely inhibits insulin-stimulated glucose disposal in humans: A randomized, placebo-controlled study

Abstract

A single dose of indinavir acutely decreases total and non-oxidative insulin-stimulated glucose disposal during a euglycemic, hyperinsulinemic clamp. Our data are compatible with the hypothesis that an acute effect of indinavir on glucose disposal in humans is mediated by a direct blockade of GLUT-4 transporters.

Metabolic Effects of Darunavir/Ritonavir Versus Atazanavir/Ritonavir in Treatment-Naive, HIV Type 1-Infected Subjects over 48 Weeks

“…In contrast to some other PIs, 8,10,11 no clinically significant changes were seen in insulin sensitivity in either the DRV/r or ATV/r arm of this study. Treatment with indinavir and treatment with LPV/r have both been associated with the development of insulin resistance in healthy subjects [9][10][11] ; however, other studies have demonstrated that LPV/r does not affect insulin sensitivity in healthy subjects.…”

“…In contrast to some other PIs, 8,10,11 no clinically significant changes were seen in insulin sensitivity in either the DRV/r or ATV/r arm of this study. Treatment with indinavir and treatment with LPV/r have both been associated with the development of insulin resistance in healthy subjects [9][10][11] ; however, other studies have demonstrated that LPV/r does not affect insulin sensitivity in healthy subjects. 12,13 Atazanavir has generally had little effect on insulin sensitivity in previous trials of HIV-negative subjects, 10,12 and switching from other PI-based therapies to ATV/r has been shown to improve insulin sensitivity in HIV-1-infected subjects.…”

“…[4][5][6][7] Additionally, some PIs have been associated with insulin resistance in HIV-negative healthy volunteers. [8][9][10][11] However, this association with insulin resistance seems to be ARV-specific, as opposed to class-specific, as studies evaluating other PIs have failed to demonstrate such an association. 12,13 The metabolic complications associated with PI-based therapy can develop within the first week after treatment initiation.…”

Insulin resistance induced by antiretroviral drugs: Current understanding of molecular mechanisms

“…17 Moreover, the incidence of insulin resistance in HIV-positive patients is significantly higher in HPI-treated patients than in patients treated with NRTIs or NNRTIs, 18 even when one considers related factors such as demography and virology. 19 Furthermore, HPIs have been shown to induce insulin resistance in seronegative patients and in animal models, [20][21][22][23] implying a clear link between HPI use and insulin resistance. However, the underlying precise mechanisms have yet to be elucidated.…”

“…The studies reviewed above suggest that the effects of HPI occur downstream in the insulin signalling pathway in 3T3-L1 adipocytes, in rats and humans, 21,22,24 possibly at the level of PKB/Akt activation and beyond. However, there is evidence that HPIs possibly act at a more proximal level of the insulin signalling pathway.…”