Premium
Farnesoid X receptor interacts with cAMP response element binding protein to modulate glucagon‐like peptide‐1 (7–36) amide secretion by intestinal L cell
Author(s) -
Li Pengzhou,
Zhu Liyong,
Yang Xiangwu,
Li Weizheng,
Sun Xulong,
Yi Bo,
Zhu Shaihong
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.27940
Subject(s) - creb , farnesoid x receptor , proglucagon , secretion , microbiology and biotechnology , endocrinology , medicine , biology , enteroendocrine cell , signal transduction , proprotein convertase , glucagon like peptide 1 , chemistry , nuclear receptor , transcription factor , hormone , biochemistry , type 2 diabetes , diabetes mellitus , ldl receptor , gene , lipoprotein , endocrine system , cholesterol
Type II diabetes is a complex, chronic, and progressive disease. Glucagon‐like peptide‐1 (7–36) amide (GLP‐1) is a gut hormone released from the L cells which stimulate insulin secretion and promotes insulin gene expression and β‐cell growth and differentiation. Elevated levels of hormones secreted by L cells are an essential reason for diabetes improvement. GLP‐1 secretion has been reported to be regulated by farnesoid X receptor (FXR), a transcriptional sensor for bile acids which also acts on glucose metabolism. Herein, we attempted to evaluate the effect of FXR on GLP‐1 secretion in mouse enteroendocrine L cell line, namely STC‐1, and to investigate the underlying mechanism. FXR inversely regulated GLP‐1 secretion in STC‐1. A total of 24 nonredundant human proteins were shown to be related to FXR by BioGRID; KEGG pathway analysis revealed that FXR was related to glucagon signaling pathway, particularly with the transcriptional activators CREB, PGC1α, Sirt1, and CBP. CREB could positively regulate GLP‐1 secretion in STC‐1 cells. FXR combined with CREB to inhibit its transcriptional activity, thus inhibiting proprotein convertase subtilisin/kexin type 1 protein level and GLP‐1 secretion. In the present study, we demonstrated a negative regulation of GLP‐1 secretion by FXR in L cell line, STC‐1; FXR exerts its function in L cells through interacting with CREB, a crucial transcriptional regulator of cAMP–CREB signaling pathway, to inhibit its transcriptional activity. Targeting FXR to rescue GLP‐1 secretion may be a promising strategy for type II diabetes.