Cammalleri C, Colby-Germinario SP, Germinario RJ; Conference on Retroviruses and Opportunistic Infections.

Program Abstr 8th Conf Retrovir Oppor Infect Conf Retrovir Oppor Infect 8th 2001 Chic Ill. 2001 Feb 4-8; 8: 244 (abstract no. 664).

SMBD Jewish Gen Hosp.

Background: We have investigated the use of protease inhibitors (PI) on basal and insulin-stimulated triglyceride synthesis (TGS) using 3H-oleate and 14C-D-glucose as precursors. Methods: The 3T3 L1 adipocyte and the L6 myotube cell lines were used. The PI employed included Ritonavir (R), Indinavir (I), and Saquinavir (S) at varying concentrations. Results: While the effects of PI on TGS were seen throughout the adipocyte induction period, the peak effects were seen 3 days post induction. A significant increase in TGS (P < 0.05, n = 3) was observed for S and I from 0.1 micromolar to 10 micromolar PI. The stimulation ratios (i.e. PI/control) ranged from 1.5 to 1.75 for S and from 1.25 to 2.0 for I. For R, the ratios were 1.2 at 1.0 micromolar R and 2.0 at 10 micromolar R. In the preceding experiments, the stimulation ratios of TGS effected by 32 nM insulin were blunted in all cases by the PI employed. For example, the insulin/control ratio (i.e. no I) was 5.9 +/- 0.6. On I exposure for 7 days, the ratio was 3.65 +/- 0.1 micromolar drug. The lack of additivity seen for insulin- and PI-induced TGS suggests involvement of similar pathways. In another series of experiments employing L6 myotubes, 1.0 micromolar S was shown to increase triglyceride synthesis, exhibiting an increase of more than 2-fold in fully differentiated myotubes. Lower concentrations of S (e.g. 0.01 micromolar and 0.1 micromolar) did not affect TGS. At 1.0 micromolar S, the average S/control TGS stimulation ratio was 1.6, while the ratio observed with 1.0 micromolar R was 1.38. The insulin/control ratio with no drug was 1.22 +/- 0.02 (n = 3), while the ratios observed with insulin + S or R were 1.7 and 1.5, respectively. Conclusions: The apparent additivity of the PI response in L6 myotubes suggests that different pathways may be effected. In summary, the data indicate that while both cell types increase TGS in response to PI exposure, the mechanism(s) involved may be different.

Publication Types:

• Meeting Abstracts

Keywords:

• Adipocytes
• Glucose
• Glucose Transporter Type 1
• Glucose Transporter Type 3
• Glucose Transporter Type 4
• Indinavir
• Insulin
• Insulin Resistance
• Muscle Fibers
• Neoplasm Proteins
• Protease Inhibitors
• Proto-Oncogene Proteins c-akt
• Ritonavir
• Saquinavir
• TM4SF1 protein, human
• Triglycerides

Other ID:

• GWAIDS0006952

UI: 102244448

From Meeting Abstracts