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http://purl.uniprot.org/citations/24356748http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/24356748http://www.w3.org/2000/01/rdf-schema#comment"

Aims/hypothesis

Glucagon-like peptide-1 (GLP-1), secreted by the enteroendocrine L cell, is an incretin hormone that potently stimulates insulin secretion. Although signalling pathways promoting GLP-1 release are well characterised, the mechanisms by which GLP-1-containing granules fuse to the L cell membrane are unknown. As soluble NSF attachment proteins (SNAREs) are known to mediate granule-membrane fusion, the role of vesicle-associated membrane proteins (VAMPs) in GLP-1 exocytosis was examined.

Methods

SNARE expression was determined in murine GLUTag L cells by RT-PCR and immunoblot and in primary murine L cells by immunofluorescence. Co-immunoprecipitation was used to examine SNARE interactions, while tetanus toxin (TetX)-mediated cleavage of VAMP was used with a GLP-1 secretion assay and total internal reflection fluorescence microscopy to determine the role of VAMP2 in exocytosis.

Results

VAMP2 was expressed in murine L cells and localised to secretory granules in GLUTag cells. VAMP1/3 and the core membrane proteins syntaxin1a and synaptosomal-associated protein 25 kDa (SNAP25) were also detected. TetX cleaved VAMPs in GLUTag cells. However, only VAMP2 interacted with syntaxin1a, as did SNAP25 and Munc18-1. TetX treatment of GLUTag cells prevented glucose-dependent insulinotrophic peptide- and oleic-acid-stimulated GLP-1 secretion (p < 0.05-0.01), as well as K(+)-stimulated single-cell exocytosis (p < 0.05-0.001), while TetX-resistant VAMP2 expression rescued GLP-1 secretion (p < 0.01-0.001).

Conclusions/interpretation

Together, these findings indicate an essential role for VAMP2 in GLP-1 exocytosis from the GLUTag L cell in response to a variety of established secretagogues. An improved understanding of the mechanisms governing the release of GLP-1 may lead to new therapeutic approaches to enhance the levels of this incretin hormone in patients with type 2 diabetes."xsd:string
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http://purl.uniprot.org/citations/24356748http://purl.uniprot.org/core/author"Zhu D."xsd:string
http://purl.uniprot.org/citations/24356748http://purl.uniprot.org/core/author"Gaisano H.Y."xsd:string
http://purl.uniprot.org/citations/24356748http://purl.uniprot.org/core/author"Brubaker P.L."xsd:string
http://purl.uniprot.org/citations/24356748http://purl.uniprot.org/core/author"Li S.K."xsd:string
http://purl.uniprot.org/citations/24356748http://purl.uniprot.org/core/date"2014"xsd:gYear
http://purl.uniprot.org/citations/24356748http://purl.uniprot.org/core/name"Diabetologia"xsd:string
http://purl.uniprot.org/citations/24356748http://purl.uniprot.org/core/pages"809-818"xsd:string
http://purl.uniprot.org/citations/24356748http://purl.uniprot.org/core/title"Role of vesicle-associated membrane protein 2 in exocytosis of glucagon-like peptide-1 from the murine intestinal L cell."xsd:string
http://purl.uniprot.org/citations/24356748http://purl.uniprot.org/core/volume"57"xsd:string
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