상세 정보

underline
Metadata Downloads : dc(xml) or Excel
Cited 0 time in scopus ci

Title 

Selective novel inverse agonists for human GPR43 augment GLP-1 secretion

 

인간 GPR43에 선택적인 신규 저해제에 의한 GLP-1 분비의 증가

Authors 

Bi Oh ParkSeong Heon KimGye Yeong KongDa Hui KimM S KwonSu Ui LeeMun-Ock KimSungchan ChoSangku LeeHyun-Jun LeeS B HanY S KwakS B LeeSunhong Kim

Publisher 

Elsevier

Issue Date 

2016

Citation 

European Journal of Pharmacology, vol. 771, no. 0, pp. 1-9

Keywords 

BTI-A-202BTI-A-404GLP-1GPR43Inverse agonistSCFA

Abstract 

GPR43/Free Fatty Acid Receptor 2 (FFAR2) is known to be activated by short-chain fatty acids and be coupled to Gi and Gq family of heterotrimeric G proteins. GPR43 is mainly expressed in neutrophils, adipocytes and enteroendocrine cells, implicated to be involved in inflammation, obesity and type 2 diabetes. However, several groups have reported the contradictory data about the physiological functions of GPR43, so that its roles in vivo remain unclear. Here, we demonstrate that a novel compound of pyrimidinecarboxamide class named as BTI-A-404 is a selective and potent competitive inverse agonist of human GPR43, but not the murine ortholog. Through structure-activity relationship (SAR), we also found active compound named as BTI-A-292. These regulators increased the cyclic AMP level and reduced acetate-induced cytoplasmic Ca2+ level. Furthermore, we show that they modulated the downstream signaling pathways of GPR43, such as ERK, p38 MAPK, and NF-κB. It was surprising that two compounds augmented the secretion of glucagon-like peptide 1 (GLP-1) in NCI-H716 cell line. Collectively, these novel and specific competitive inhibitors regulate all aspects of GPR43 signaling and the results underscore the therapeutic potential of them.

ISSN 

0014-2999

Link 

http://dx.doi.org/10.1016/j.ejphar.2015.12.010

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


There are no files associated with this item.
qrcode

FusionCharts.
DSpace Software Coptright(c) 2010 MIT and Hewleft-Packard  /  KRIBB-REPOSITORY ( Email:jakim@kribb.re.kr)