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Am J Physiol Endocrinol Metab (May 28, 2002). doi:10.1152/ajpendo.00092.2002
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Articles in PresS, published online ahead of print May 28, 2002
Am J Physiol Endocrinol Metab, 10.1152/ajpendo.00092.2002
Submitted on March 1, 2002
Accepted on April 1, 2002

C2C12 myocytes lack an insulin responsive vesicular compartment despite dexamethasone-induced Glut4 expression

Lori L. Tortorella1 and Paul F. Pilch1*

1 Biochemistry, Boston University School of Medicine, Boston, MA, USA

* To whom correspondence should be addressed. E-mail: ppilch{at}bu.edu.

Insulin regulates the uptake of glucose into skeletal muscle and adipocytes by redistributing the tissue-specific glucose transporter, Glut4, from intracellular vesicles to the cell surface. To date, Glut4 is the only protein involved in insulin-regulated vesicular traffic that has this tissue distribution, thus raising the possibility that its expression alone may allow formation of an insulin responsive vesicular compartment. We show here that treatment of differentiating C2C12 myoblasts with dexamethasone, acting via the glucocorticoid receptor, causes at least a 10 fold increase in Glut4 expression but results in no significant change in insulin stimulated glucose transport. Signaling from the insulin receptor to its target, Akt2, and expression of the SNARE proteins, syntaxin 4 and VAMP2, are normal in dexamethasone treated C2C12 cells. However, these cells show no insulin-dependent trafficking of the insulin responsive aminopeptidase (IRAP) or the transferrin receptor, respective markers for intracellular Glut4-rich compartments and endosomes that are insulin responsive in mature muscle and adipose cells. Therefore, these data support the hypothesis that Glut4 expression, itself, is insufficient to establish an insulin sensitive vesicular compartment.




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