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This version published online on January 15, 2004
Endocrinology, doi:10.1210/en.2003-1197
A more recent version of this article appeared on April 1, 2004
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Submitted on September 10, 2003
Accepted on January 6, 2004

Annexin II is a Thiazolidinedione Responsive Gene Involved in Insulin-induced GLUT4 Translocation in 3T3-L1 Adipocytes

Jie Huang, Stanley H. Hsia, Takeshi Imamura, Isao Usui, and Jerrold M. Olefsky*

Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego, La Jolla, California 92093-0673; San Diego Veterans Administration Medical Research Service and the Whittier Institute for Diabetes, 9894 Genesee Avenue, La Jolla, CA 92037

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

The target genes of PPAR{gamma} ligands that lead to insulin sensitization are not fully understood. In this study, we have found that the thiazolidinedione (TZD), troglitazone, increases expression of annexin II at both the mRNA and protein levels, raising the possibility that annexin II plays a role in insulin-stimulated GLUT4 translocation and glucose transport. To assess this, we microinjected annexin II antibody or annexin II siRNA into 3T3-L1 adipocytes and found that insulin-stimulated GLUT4 translocation was inhibited by 54% and 60%, respectively. Furthermore, microinjection of annexin II antibody inhibited constitutively active G{alpha}q (Q209L-G{alpha}q)-induced, but not osmotic shock- induced GLUT4 translocation. When cells were co-transfected with wild-type annexin II, along with an EGFP-cmyc-GLUT4 construct, and the percentage of cells expressing cmyc-GLUT4 at the cell surface was measured by immunofluorescence microscopy, there was a marked increase in the ability of insulin to stimulate recruitment of cmyc-GLUT4 protein to the cell surface. In summary, our results show that annexin II is a newly described TZD response gene involved in insulin-induced GLUT4 translocation in 3T3-L1 adipocytes.
Key words: annexin II • thiazolidinedione (TZD) • insulin signaling • GLUT4 translocation




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