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• W2321486909 abstract "Objectives To determine the relative sensitivities of glucose transporter isoforms to the protease inhibitor indinavir and to determine the kinetic mechanism of indinavir-mediated Glut4 isoform inhibition. Methods The rate of 2-deoxyglucose uptake was measured in Xenopus laevis oocytes heterologously expressing mammalian Glut isoforms. 2-Deoxyglucose uptake was also measured in 3T3-L1 fibroblasts, 3T3-L1 adipocytes, and primary rat adipocytes. Results The sensitivity to inhibition by indinavir among the Glut isoforms as assayed in the X. laevis oocyte system was as follows in decreasing order: Glut4 ≫ Glut2 > Glut3 > Glut1 ≈ Glut8. 2-Deoxyglucose uptake measurements in insulin-stimulated primary rat adipocytes indicated a non-competitive mode of transport inhibition by indinavir under zero-trans conditions with a KI of 15 μM. Conclusions Indinavir appears to be a relatively selective inhibitor of the Glut4 isoform. As the concentration required to significantly inhibit insulin-stimulated glucose uptake in primary rat adipocytes is well within the physiologic range achieved in therapy, we conclude that direct inhibition of Glut4 contributes to the insulin resistance observed in patients receiving this drug." @default.
• W2321486909 created "2016-06-24" @default.
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• W2321486909 date "2002-04-01" @default.
• W2321486909 modified "2023-09-25" @default.
• W2321486909 title "Indinavir inhibits the glucose transporter isoform Glut4 at physiologic concentrations" @default.
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• W2321486909 doi "https://doi.org/10.1097/00002030-200204120-00005" @default.
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