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Endocrinology, doi:10.1210/en.2003-1197
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Endocrinology Vol. 145, No. 4 1579-1586
Copyright © 2004 by The Endocrine Society

Annexin II Is a Thiazolidinedione-Responsive Gene Involved in Insulin-Induced Glucose Transporter Isoform 4 Translocation in 3T3-L1 Adipocytes

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

Department of Medicine (J.H., S.H.H., T.I., I.U., J.M.O.), Division of Endocrinology and Metabolism, University of California, San Diego, La Jolla, California 92093; and San Diego Veterans Administration Medical Research Service and the Whittier Institute for Diabetes (J.M.O.), La Jolla, California 92037

Address all correspondence and requests for reprints to: Jerrold M. Olefsky, M.D., Department of Medicine (0673), University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0673. E-mail: jolefsky{at}ucsd.edu.

The target genes of peroxisomal proliferator-activated receptor-{gamma} ligands that lead to insulin sensitization are not fully understood. In this study, we have found that the thiazolidinedione, 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 glucose transporter isoform 4 (GLUT4) translocation and glucose transport. To assess this, we microinjected annexin II antibody or annexin II small interfering RNA 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 cotransfected with wild-type annexin II, along with an enhanced green fluorescent protein-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 thiazolidinedione response gene involved in insulin-induced GLUT4 translocation in 3T3-L1 adipocytes.




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