Intracellular insulin-responsive glucose transporter (GLUT4) distribution but not insulin-stimulated GLUT4 exocytosis and recycling are microtubule dependent

Satoshi Shigematsu, Ahmir H. Khan, Makoto Kanzaki, Jeffrey E. Pessin

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

To investigate the potential role of microtubules in the regulation of insulin-responsive glucose transporter (GLUT4) trafficking in adipocytes, we examined the effects of microtubule depolymerizing and stabilizing agents. In contrast to previous reports, disruption or stabilization of microtubule structures had no significant effect on insulin-stimulated GLUT4 translocation. However, consistent with a more recent study (Molero, J. C., J. P. Whitehead, T. Meerloo, and D. E. James, 2001, J Biol Chem 276:43829-43835) nocodazole did inhibit glucose uptake through a direct interaction with the transporter itself independent of the translocation process. In addition, the initial rate of GLUT4 endocytosis was not significantly affected by microtubule depolymerization. However, these internalized GLUT4 compartments are confined to regions just beneath the plasma membrane and were not exposed to the extracellular space. Furthermore, they were unable to undergo further sorting steps and trafficking to the perinuclear region. Nevertheless, these apparent early endocytic GLUT4 compartments fully responded to a second insulin stimulation with an identical extent of plasma membrane translocation. Together, these data demonstrate that although microtubular organization may play a role in the trafficking of GLUT4 early endocytic vesicles back to the perinuclear region, they do not have a significant role in insulin-stimulated GLUT4 exocytosis, initial endocytosis from the plasma membrane and/or recycling back to the plasma membrane.

Original languageEnglish (US)
Pages (from-to)1060-1068
Number of pages9
JournalMolecular Endocrinology
Volume16
Issue number5
DOIs
StatePublished - 2002
Externally publishedYes

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Glucose Transporter Type 4
Exocytosis
Recycling
Microtubules
Cell Membrane
Insulin
Endocytosis
Nocodazole
Transport Vesicles
Excipients
Extracellular Space
Adipocytes
Glucose

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

Intracellular insulin-responsive glucose transporter (GLUT4) distribution but not insulin-stimulated GLUT4 exocytosis and recycling are microtubule dependent. / Shigematsu, Satoshi; Khan, Ahmir H.; Kanzaki, Makoto; Pessin, Jeffrey E.

In: Molecular Endocrinology, Vol. 16, No. 5, 2002, p. 1060-1068.

Research output: Contribution to journalArticle

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