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Differential Effects of Saquinavir on Glucose Transport in a Variety of Cell Cultures S. P. COLBY-GERMINARIO, A. BREWER, M. A. WAINBERG, and R. J. GERMINARIO*. Seri Mortimer B. Davis Jewish Gen. Hosp., McGill Univ., Concordia Univ., Montreal, Quebec, Canada We have investigated. the effects of the protease inhibitor Saquinavir (S) on basal and insulin-stimulated sugar transport using 3H-deoxy-D-glucose (DG) (0.05 mM) as the transportable substrate. Several cell culture model systems, such as: 1) human fibroblasts (HF) (connective tissue), 2) the 3T3 L1 preadipocyte (3T3) (fat cell) and 3) the L6 myoblast/myotube (L6) (muscle cell), were employed. HF were exposed to ±1mM S (~7–10 days). In cells not exposed to S, the insulin (667nM):control (I:C) transport ratio was 1.48±.11 while in the S-exposed group, the I:C ratio was 0.8±.23. The decreased insulin transport stimulation in the S-exposed HF was related to a significant increase (two-tailed t-test, P < 0.01, n=4) in basal glucose transport in the S-exposed vs control groups, respectively (1.23±0.25 vs 0.76±0.32 nmoles DG/mg/protein/5 min). The effect of S on similar parameters in the L6 myoblast cell line during myotube induction (5 days) was studied over 10nM to 1mM S and 67nM insulin was the stimulating dose. No differences were observed in the I:C ratios (2.05±.12-control to 2.2±.42-1mM S) over all concentrations of S used (One Way ANOVA; P > 0.05, n=4). Also, specific insulin binding was determined in all groups of L6±S with no differences being observed (One Way ANOVA; P > 0.05, n=4). Subsequently, the 3T3 adipocyte was studied employing S from 10nM to 1mM during adipocyte induction (10 days). At 67nM insulin, no differences in I:C ratios or basal sugar transport rates were observed (One Way ANOVA: P>0.05, n=4). The data indicate that cells representative of different tissues in vivo respond differently to the protease inhibitor S and studies of combinations of other protease inhibitors with nucleoside and/or nonnucleoside reverse transcriptase inhibitors could help elucidate the site(s) involved in treatment-related complications in AIDS. Key Words: different cell cultures, insulin responses, saquinavir effect |
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© 7th
Conference on Retroviruses and Opportunistic Infections, |