Essential Role of Syntaxin-Binding Protein-1 in the Regulation of Glucagon-Like Peptide-1 Secretion.

Endocrinology
Jhenielle R CampbellPatricia L Brubaker

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 exocy...Continue Reading

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Citations

Sep 22, 2020·Endocrinology·Alexandre MartchenkoPatricia L Brubaker
Apr 13, 2021·Journal of Peptide Science : an Official Publication of the European Peptide Society·Galyna V GrahamPeter R Flatt
Jun 8, 2021·Frontiers in Endocrinology·Ryan A LaffertyPeter R Flatt

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Datasets Mentioned

BETA
GSE114853
GSE114913

Methods Mentioned

BETA
Assay
ELISA
RNA-seq
transgenic
PCR
immunoprecipitation

Software Mentioned

JTK
Excel
Elements Imaging
GraphPad Prism
NIS
_ CYCLE

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