alexa Indinavir acutely inhibits insulin-stimulated glucose disposal in humans: a randomized, placebo-controlled study.
Infectious Diseases

Infectious Diseases

Journal of AIDS & Clinical Research

Author(s): Noor MA, Seneviratne T, Aweeka FT, Lo JC, Schwarz JM,

Abstract Share this page

Abstract BACKGROUND: Therapy with HIV protease inhibitors (PI) causes insulin resistance even in the absence of HIV infection, hyperlipidemia or changes in body composition. The mechanism of the effects on insulin action is unknown. In vitro studies suggest that PI selectively and rapidly inhibit the activity of the insulin-responsive glucose transporter GLUT-4. We hypothesized that a single dose of the PI indinavir resulting in therapeutic plasma concentrations would acutely decrease insulin-stimulated glucose disposal in healthy human volunteers. METHODS: Randomized, double-blind, cross-over study comparing the effect of 1200 mg of orally administered indinavir and placebo on insulin-stimulated glucose disposal during a 180-min euglycemic, hyperinsulinemic clamp. Six healthy HIV-seronegative adult male volunteers were studied twice with 7 to 10 days between studies. RESULTS: There were no significant differences in baseline fasting body weight, or plasma glucose, insulin, lipid and lipoprotein levels between placebo- and indinavir-treated subjects. During steady-state (t60-180 min) insulin reached comparable levels (394 +/- 13 versus 390 +/- 11 pmol/l) and glucose was clamped at approximately 4.4 mmol/l under both conditions. The average maximum concentration of indinavir was 9.4 +/- 2.2 microM and the 2-h area under the curve was 13.5 +/- 3.1 microM.h. Insulin-stimulated glucose disposal per unit of insulin (M/I) decreased in all subjects from 14.1 +/- 1.2 to 9.2 +/- 0.8 mg/kg.min per microUI/ml (95\% confidence interval for change, 3.7-6.1; P < 0.001) on indinavir (average decrease, 34.1 +/- 9.2\%). The non-oxidative component of total glucose disposal (storage) decreased from 3.9 +/- 1.8 to 1.9 +/- 0.9 mg/kg.min (P < 0.01). Free fatty acid levels were not significantly different at baseline and were suppressed equally with insulin administration during both studies. CONCLUSIONS: 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.
This article was published in AIDS and referenced in Journal of AIDS & Clinical Research

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords