Role of Vesicle-associated Membrane Protein 2 in Glucagon-like Peptide-1 Secretion

Glucagon-like peptide-1 (GLP-1) is an incretin hormone produced by the enteroendocrine L-cell that potently stimulates insulin secretion. Although signaling pathways promoting GLP-1 secretion are well characterized, the mechanism by which GLP-1 containing granules fuse to the L-cell membrane remain elusive. RT-PCR and protein analysis indicate that vesicle-associated membrane protein 2 (VAMP2) is expressed and localized to secretory granules in the murine GLUTag L-cell model. VAMP2, but not VAMP1, interacted with the core SNARE complex protein, Syntaxin 1a, in GLUTag cells. Tetanus toxin (TetX) cleavage of VAMP2 in GLUTag cells prevented glucose-dependent insulinotropic peptide (GIP)- and oleic acid (OA)-stimulated GLP-1 secretion, as well as K+-stimulated exocytosis from GLUTag cells. Although components of membrane rafts were detected in GLUTag cells, their role in GLP-1 secretion remains to be determined. Together, these findings indicate an essential role for VAMP2 in GLP-1 exocytosis from the GLUTag cell.MAS