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Essential role of syntaxin-binding protein-1 in the regulation of glucagon-like peptide-1 secretion

Published version
Peer-reviewed

Change log

Authors

Campbell, Jhenielle R 
Martchenko, Alexandre 
Sweeney, Maegan E 
Maalouf, Michael F 

Abstract

Circadian secretion of the incretin, glucagon-like peptide-1 (GLP-1), correlates with expression of the core clock gene, Bmal1, in the intestinal L-cell. Several SNARE proteins known to be circadian in pancreatic α- and β-cells are also necessary for GLP-1 secretion. However, the role of the accessory SNARE, Syntaxin binding protein-1 (Stxbp1; also known as Munc18-1) in the L-cell is unknown. The aim of this study was to determine whether Stxbp1 is under circadian regulation in the L-cell and its role in the control of GLP-1 secretion. Stxbp1 was highly-enriched in L-cells, and STXBP1 was expressed in a subpopulation of L-cells in mouse and human intestinal sections. Stxbp1 transcripts and protein displayed circadian patterns in mGLUTag L-cells line, while chromatin-immunoprecipitation revealed increased interaction between BMAL1 and Stxbp1 at the peak time-point of the circadian pattern. STXBP1 recruitment to the cytosol and plasma membrane within 30 minutes of L-cell stimulation was also observed at this time-point. Loss of Stxbp1 in vitro and in vivo led to reduced stimulated GLP-1 secretion at the peak time-point of circadian release, and impaired GLP-1 secretion ex vivo. In conclusion, Stxbp1 is a circadian regulated exocytotic protein in the intestinal L-cell that is an essential regulatory component of GLP-1 secretion.

Description

Keywords

GLP-1, Munc18-1, SNARE, Stxbp1, enteroendocrine, exocytosis, glucagon, ARNTL Transcription Factors, Animals, Cell Line, Cell Membrane, Circadian Rhythm, Enteroendocrine Cells, Exocytosis, Glucagon-Like Peptide 1, Humans, Ileum, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Munc18 Proteins, Protein Binding

Journal Title

Endocrinology

Conference Name

Journal ISSN

0013-7227
1945-7170

Volume Title

161

Publisher

Oxford University Press
Sponsorship
Medical Research Council (MC_UU_12012/3)
Wellcome Trust (106262/Z/14/Z)
Wellcome Trust (100574/Z/12/Z)
Medical Research Council (MC_UU_12012/5)
MRC (MC_UU_00014/3)
MRC (MC_UU_00014/5)
Medical Research Council (MC_PC_12012)
Wellcome Trust MRC