These authors contributed equally to this work.
Mapping Insulin/GLUT4 Circuitry
Article first published online: 15 MAR 2011
© 2011 John Wiley & Sons A/S
Volume 12, Issue 6, pages 672–681, June 2011
How to Cite
Rowland, A. F., Fazakerley, D. J. and James, D. E. (2011), Mapping Insulin/GLUT4 Circuitry. Traffic, 12: 672–681. doi: 10.1111/j.1600-0854.2011.01178.x
- Issue published online: 9 MAY 2011
- Article first published online: 15 MAR 2011
- Accepted manuscript online: 25 FEB 2011 02:44AM EST
- Received 9 January 2011, revised and accepted for publication 18 February 2011, uncorrected manuscript published online 25 February 2011, published online 15 March 2011
One of the most important metabolic actions of insulin is catalysing glucose uptake into skeletal muscle and adipose tissue. This is accomplished via activation of the phosphatidylinositol-3-kinase/Akt signalling pathway and subsequent translocation of GLUT4 from intracellular storage vesicles to the plasma membrane. As such, this represents an ideal system for studying the convergence of signal transduction and protein trafficking. The GLUT4 translocation process is complex, but can be dissected into at least four discrete trafficking steps. This raises the question as to which of these is the major regulated step in insulin-stimulated GLUT4 translocation. Numerous molecules have been reported to regulate GLUT4 trafficking. However, with the exception of TBC1D4, the molecular details of these distal signalling arms of the insulin signalling network and how they modify distinct steps of GLUT4 trafficking have not been established. We discuss the need to adopt a more global approach to expand and deepen our understanding of the molecular processes underpinning this system. Strategies that facilitate the generation of detailed models of the entire insulin signalling network will enable us to identify the critical nodes that control GLUT4 traffic and decipher emergent properties of the system that are not currently apparent.