Regulation of glucose transporter 4 traffic by energy deprivation from mitochondrial compromise
Article first published online: 19 FEB 2009
© 2009 The Authors. Journal compilation © 2009 Scandinavian Physiological Society
Special Issue: THE 5TH INTERNATIONAL SYMPOSIUM ON AMPK 'AMPK IN SICKNESS AND HEALTH - FROM MOLECULE TO MAN'
Volume 196, Issue 1, pages 27–35, May 2009
How to Cite
Klip, A., Schertzer, J. D., Bilan, P. J., Thong, F. and Antonescu, C. (2009), Regulation of glucose transporter 4 traffic by energy deprivation from mitochondrial compromise. Acta Physiologica, 196: 27–35. doi: 10.1111/j.1748-1716.2009.01974.x
- Issue published online: 1 APR 2009
- Article first published online: 19 FEB 2009
- Received 21 September 2008, accepted 5 December 2008
Skeletal muscle is the major store and consumer of fatty acids and glucose. Glucose enters muscle through glucose transporter 4 (GLUT4). Upon insufficient oxygen availability or energy compromise, aerobic metabolism of glucose and fatty aids cannot proceed, and muscle cells rely on anaerobic metabolism of glucose to restore cellular energy status. An increase in glucose uptake into muscle is a key response to stimuli requiring rapid energy supply. This chapter analyses the mechanisms of the adaptive regulation of glucose transport that rescue muscle cells from mitochondrial uncoupling. Under these conditions, the initial drop in ATP recovers rapidly, through a compensatory increase in glucose uptake. This adaptive response involves AMPK activation by the initial ATP drop, which elevates cell surface GLUT4 and glucose uptake. The gain in surface GLUT4 involves different signals and routes of intracellular traffic compared with those engaged by insulin. The hormone increases GLUT4 exocytosis through phosphatidylinositol 3-kinase and Akt, whereas energy stress retards GLUT4 endocytosis through AMPK and calcium inputs. Given that energy stress is a component of muscle contraction, and that contraction activates AMPK and raises cytosolic calcium, we hypothesize that the increase in glucose uptake during contraction may also involve a reduction in GLUT4 endocytosis.