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Papers In Press, published online ahead of print September 16, 2002
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Submitted on June 24, 2002
Lady Davis Institute, SMBD-Jewish General Hospital, Montreal, Quebec H3T 1E2
Corresponding Author: ralph.germinario{at}mcgill.ca
The objective of our research was to investigate the effects of the protease Inhibitors Ritonavir, Saquinavir and Indinavir on triglyceride synthesis, lipolysis,insulin binding and signaling in differentiating 3T3 L-1 pre-adipocytes. Saquinavir(S), Ritonavir (R) and Indinavir(I) all stimulated basal triglyceride(TG) synthesis. Also, all concentrations of protease inhibitors employed (i.e. 0.1µM to 10µM) significantly decreased insulin- stimulated TG synthesis. No effects of any of the protease inhibitors were observed either on basal lipolysis or after stimulation of lipolysis with 100 nM nor adrenaline. Specific 125I-insulin binding was observed to be decreased by exposure to all the protease inhibitors throughout the period of adipocyte phenotype development. This was mediated by Ind through a receptor decrease with no effects on receptor affinity. During differentiation with R (i.e.1- 11 days post addition of differentiating cocktail), insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation was ascertained (day 11) and found to be decreased in the R exposed cells when compared to control cells. The results reported herein demonstrate protease inhibitor effects on basal TG synthesis while exhibiting decreased insulin-stimulated TG synthesis at physiological concentrations of protease inhibitors. These effects may be subsequent to decreased insulin binding and/or IRS-1 tyrosine phosphorylation.
Revised on August 30, 2002
Accepted on September 11, 2002
The effects of protease inhibitors on basal and insulin-stimulated lipid metabolism, insulin binding and signaling
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