Abstract

Introduction

Materials & Methods

Results

Discussion & Conclusion

References

Discussion
Board

The acute stimulation of glucose uptake by insulin in fat and muscle cells is primarily the result of translocation of GLUT4 facilitative glucose transporters from an internal compartment to the plasma membrane. Proteolytic cleavage of VAMP-2 and antibody neutralization of syntaxin-4 decrease both insulin-stimulated glucose uptake and GLUT4 appearance at the cell surface. Here, we investigate the role of a third SNARE protein, SNAP23, in GLUT4 translocation and glucose uptake. In vitro binding studies demonstrated that SNAP23 binds VAMP-2 and syntaxin-4 in binary combinations and with high affinity but does not appear able to form a stable, SDS-resistant complex with them. Microinjection of a polyclonal antibody to the C-terminus of SNAP23 inhibited insulin-stimulated GLUT4 incorporation into the membrane, while microinjection of full length recombinant SNAP23 enhanced insulin stimulation of this process. Introduction of recombinant SNAP23 into chemically permeabilized 3T3-L1 adipocytes also enhanced insulin-stimulated glucose transport. These results indicate that SNAP23 is required for insulin-dependent, functional incorporation of GLUT4 into the plasma membrane, and therefore appears to be a fusion catalyst along with syntaxin-4 and VAMP-2 Furthermore, the endogenous content of SNAP23 may be rate limiting in this process.

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Presentation Number SAfoster0710
Keywords: glucose transport, SNARE, SNAP23, GLUT4, insulin