7th Conference on Retroviruses and Opportunistic Infections


San Francisco, CA - January 30 -February 4, 2000



DIFFERENTIAL EFFECTS OF SAQUINAVIR ON GLUCOSE TRANSPORT IN A VARIETY OF CELL CULTURES.

Conf Retroviruses Opportunistic Infect 2000 Jan 30-Feb 2; 7:82 (abstract no. 40)

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 ± 1µM S (approximately 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 1µM S and 67nM insulin was the stimulating dose. No differences were observed in the I:C ratios (2.05 ± .12-control to 2.2 ± .42-1µM 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 1µM 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.

Keywords: AEGIS, Monosaccharide Transport Proteins, Saquinavir, Glucose, Insulin, Adipocytes, Biological Transport, Cell Line, Hypoglycemic Agents, Blood Glucose, Insulin Resistance, Glucose-6-Phosphate, Glucose-6-Phosphatase, Fibroblasts, Human, AIDS

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2000-01-30
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