Abstract

Introduction

Early signalling molecules

Intracellular GLUT4 compartments

Targeting and fusion of GLUT4 vesicles

References

Discussion
Board

One of the major actions of insulin in fat and skeletal muscle is to cause an acute acceleration in glucose transport (GT). This stimulation in GT is principally due to the rapid redistribution of the GLUT4 glucose transporter from an intracellular vesicular pool to the cell surface. One of our major interests is to try and understand the nature of the intracellular GLUT4 compartment in skeletal muscle and to develop some insight into how GLUT4 vesicles may be targeted and fused with the sarcolemma. Using subcellular fractionation and immunoprecipitation techniques we have identified the presence of two distinct intracellular GLUT4 compartments. One of these compartments is enriched with the transferrin receptor (TfR) and IRAP (vp165), but does not appear to show any net loss in GLUT4 following insulin treatment. The second compartment is devoid of TfR, but possesses both IRAP and Rab4. Following insulin treatment, this latter compartment shows a marked reduction in GLUT4 content, which is recovered in the sarcolemma suggesting that it represents the insulin-regulated pool. Surprisingly, the two vSNARE proteins, cellubrevin and VAMP2, which some investigators have suggested play a role in the fusion of GLUT4 vesicles with the plasma membrane in fat cells were undetectable in either of the two GLUT4 compartments in skeletal muscle. We propose that the fusion of GLUT4 vesicles with the sarcolemma is either dependent on some other, as yet uncharacterised vSNARE, or that the mechanism by which muscle GLUT4 vesicles fuse with the sarcolemma may be fundamentally different to that proposed in fat cells.

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Presentation Number SAhajduch0481
Keywords: muscle, adipose tissue, transporter, SNARE, Rab4