Ho, Ping-Chih and Lin, Yi-Wei and Tsui, Yao-Chen and Gupta, Pawan and Wei, Li-Na (2009) A negative regulatory pathway of GLUT4 trafficking in adipocyte: new function of RIP140 in the cytoplasm via AS160. Cell metabolism, 10 (6). pp. 516-23. ISSN 1932-7420
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Abstract
Receptor-interacting protein 140 (RIP140), a nuclear receptor corepressor, is important for lipid and glucose metabolism. In adipocytes, RIP140 can be phosphorylated by protein kinase C epsilon (PKCvarepsilon), followed by arginine methylation, and exported to the cytoplasm. This study demonstrates for the first time a cytoplasmic function for RIP140: to counteract insulin-stimulated glucose transporter 4 (GLUT4) membrane partitioning and glucose uptake in adipocytes. Cytoplasmic RIP140 interacts with the Akt substrate AS160, thereby impeding AS160 phosphorylation by Akt; this in turn reduces GLUT4 trafficking. This signal transduction pathway can be recapitulated in the epididymal adipocytes of diet-induced obese mice: nuclear PKCvarepsilon is activated, cytoplasmic RIP140 increases, and GLUT4 trafficking and glucose uptake are reduced. The data reveal a new, cytoplasmic function for RIP140 as a negative regulator of GLUT4 trafficking and glucose uptake, and shed insight into the regulation of basal and insulin-stimulated glucose disposal by a nuclear-initiated counteracting mechanism.
| Item Type: | Article |
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| Additional Information: | Copyright of this article belongs to Cell Press |
| Uncontrolled Keywords: | GLUT4; cytoplasmic RIP140; adipocytes; AS160; Akt; post-translational modification |
| Subjects: | Q Science > QR Microbiology |
| Depositing User: | Dr. K.P.S.Sengar |
| Date Deposited: | 28 Feb 2012 16:11 |
| Last Modified: | 28 Feb 2012 16:11 |
| URI: | http://crdd.osdd.net/open/id/eprint/1087 |
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