Nocodazole inhibits insulin-stimulated glusocs transport in 3T3-L1 adipocytes via a microtubule independant mechanism

Molero, Juan Carlos, Whitehead, Jonathan P., Meerloo, Timo and James, David E. 2001, Nocodazole inhibits insulin-stimulated glusocs transport in 3T3-L1 adipocytes via a microtubule independant mechanism, Journal of biological chemistry, vol. 276, no. 47, pp. 43829-43835, doi: 10.1074/jbc.M105452200.

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Title Nocodazole inhibits insulin-stimulated glusocs transport in 3T3-L1 adipocytes via a microtubule independant mechanism
Author(s) Molero, Juan Carlos
Whitehead, Jonathan P.
Meerloo, Timo
James, David E.
Journal name Journal of biological chemistry
Volume number 276
Issue number 47
Start page 43829
End page 43835
Publisher American Society for Biochemistry and Molecular Biology
Place of publication Baltimore, Md.
Publication date 2001-09-24
ISSN 0021-9258
Summary Insulin stimulates glucose transport in adipocytes and muscle cells by triggering redistribution of the GLUT4 glucose transporter from an intracellular perinuclear location to the cell surface. Recent reports have shown that the microtubule-depolymerizing agent nocodazole inhibits insulin-stimulated glucose transport, implicating an important role for microtubules in this process. In the present study we show that 2 µM nocodazole completely depolymerized microtubules in 3T3-L1 adipocytes, as determined morphologically and biochemically, resulting in dispersal of the perinuclear GLUT4 compartment and the Golgi apparatus. However, 2 µM nocodazole did not significantly effect either the kinetics or magnitude of insulin-stimulated glucose transport. Consistent with previous studies, higher concentrations of nocodazole (10-33 µM) significantly inhibited basal and insulin-stimulated glucose uptake in adipocytes. This effect was not likely the result of microtubule depolymerization because in the presence of taxol, which blocked nocodazole-induced depolymerization of microtubules as well as the dispersal of the perinuclear GLUT4 compartment, the inhibitory effect of 10-33 µM nocodazole on insulin-stimulated glucose uptake prevailed. Despite the decrease in insulin-stimulated glucose transport with 33 µM nocodazole we did not observe inhibition of insulin-stimulated GLUT4 translocation to the cell surface under these conditions. Consistent with a direct effect of nocodazole on glucose transporter function we observed a rapid inhibitory effect of nocodazole on glucose transport activity when added to either 3T3-L1 adipocytes or to Chinese hamster ovary cells at 4 °C. These studies reveal a new and unexpected effect of nocodazole in mammalian cells which appears to occur independently of its microtubule-depolymerizing effects.
Language eng
DOI 10.1074/jbc.M105452200
Field of Research 060199 Biochemistry and Cell Biology not elsewhere classified
Socio Economic Objective 970106 Expanding Knowledge in the Biological Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2001, American Society for Biochemistry and Molecular Biology, Inc.
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Document type: Journal Article
Collection: School of Exercise and Nutrition Sciences
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