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Mapping the insulin/GLUT4 circuitry


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 PI3K/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 4 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.

Authors Rowland, A. F.; Fazakerley, D. J.; James, D. E.:
Publisher Name TRAFFIC
Published Date 2011-05-01
Published Volume 12
Published Issue 6
Published Pages 672-81
Status Published in-print
DOI 10.1111/j.1600-0854.2011.01178.x
URL link to publisher's version
OpenAccess link to author's accepted manuscript version