Editors' ChoicePhysiology

HIV Protease Inhibitors Block Glut4 Activity

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Science's STKE  11 Jul 2000:
Vol. 2000, Issue 40, pp. tw1
DOI: 10.1126/stke.2000.40.tw1

HIV protease inhibitor therapy, although beneficial to AIDS patients, often results in serious side effects with long-term administration. Frequently, patients develop insulin resistance that leads to type 2 diabetes. Murata et al. studied the effects of indinavir, an HIV protease inhibitor, on glucose transport and found that glucose uptake is severely reduced. Cells treated with indinavir did not exhibit defective insulin signaling, as measured by protein tyrosine phosphorylation, and translocation of the glucose transporters Glut1 and Glut4 to the plasma membrane was normal. However, Glut4- but not Glut1-mediated glucose transport across the cell membrane was diminished. Other HIV protease inhibitors also inhibited glucose uptake in 3T3-L1 cells; however, it was not demonstrated whether these inhibitors also selectively blocked the function of Glut4. These results suggest that the design of a new generation of protease inhibitors will have to account for undesirable glucose uptake inhibition.

Murata, H., Hruz, P.W., and Mueckler, M. (2000) The mechanism of insulin resistance caused by HIV protease inhibitor therapy. J. Biol. Chem. 275: 20251-20254. [Abstract] [Full Text]

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