First published online February 18, 2009
Journal of Cell Science 122, 505e (2009)
© The Company of Biologists Limited
At the heart of GLUT4 trafficking
Glucose homeostasis in striated muscle and adipose tissue is mediated by GLUT4, a glucose transporter that translocates from intracellular compartments to external surfaces following exposure to appropriate stimuli. Dysregulation of glucose metabolism in skeletal muscle is associated with insulin resistance and, in heart muscle, might be a mortality risk factor in patients with coronary heart failure. In skeletal muscle cells, insulin and contractile activity reportedly cause different patterns of GLUT4 translocation to different membranous locations (the sarcolemma and the transverse tubules). However, working with muscle tissue is technically difficult, making the study of GLUT4 translocation a challenge. On p. 727, Geoffrey Holman and colleagues present a new mouse model that allows visualisation of GLUT4 in heart muscle without the need for cell disruption. GLUT4 that is fused to both haemaglutinin (HA) and green fluorescent protein (GFP) is expressed under the control of a muscle-specific promoter and visualised using specific antibody-based reagents and confocal microscopy. This approach shows that, in cardiomyocytes, GLUT4 translocates from intracellular compartments to the sarcolemma and transverse tubules via the same intracellular route in response to insulin, contractile activity or hypoxia, despite the activation of diverse signalling pathways by each stimulus.

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Related articles in JCS:
- A common trafficking route for GLUT4 in cardiomyocytes in response to insulin, contraction and energy-status signalling
- Daniel J. Fazakerley, Scott P. Lawrence, Vladimir A. Lizunov, Samuel W. Cushman, and Geoffrey D. Holman
JCS 2009 122: 727-734.
[Abstract]
[Full Text]