Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Mar 15:269:119029.
doi: 10.1016/j.lfs.2021.119029. Epub 2021 Jan 12.

A novel GPR120-selective agonist promotes insulin secretion and improves chronic inflammation

Liu Yang  1 , Xian-Tao Lei  2 , Qi Huang  3 , Ting Wang  4 , Hong-Bin Sun  5 , He-Yao Wang  6
Affiliations

A novel GPR120-selective agonist promotes insulin secretion and improves chronic inflammation

Liu Yang et al. Life Sci. .

Abstract

Aims: The present study aimed to disclose a potent and selective GPR120 agonist LXT34 and its anti-diabetic effects.

Main methods: Calcium mobilization assay was used to measure the agonistic potency and selectivity of LXT34 in GPR120 or GPR40-overexpression Chinese hamster ovary (CHO) cells. Glucagon-like peptide-1 (GLP-1) release and glucose-stimulated insulin secretion (GSIS) were evaluated in human colonic epithelial cell line NCI-H716 and mouse insulinoma cell line MIN6 by enzyme-linked immunosorbent assay (ELISA), respectively. The anti-inflammatory effect was determined in lipopolysaccharide (LPS)-induced murine macrophage cell line RAW264.7. Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed to assess the anti-diabetic effects of LXT34 in db/db mice, and chronic inflammation in liver and adipose tissues were investigated using histomorphology, immunoblot and gene expression analysis.

Key findings: LXT34 was a potent GPR120 agonist with negligible activity toward human and mouse GPR40. LXT34 could potentiate GSIS and suppress LPS-induced inflammation in macrophages. LXT34 not only markedly improved glucose tolerance and insulin resistance, but also distinctly reduced macrophages infiltration, pro-inflammatory cytokines expression and JNK phosphorylation of both liver and adipose tissues in db/db mice.

Significance: LXT34, a novel and potent GPR120-selective agonist, showed beneficial effects on improving glucose homeostasis in obesity-related type 2 diabetes.

Keywords: Anti-inflammation; GPR120 agonist; Insulin resistance; Insulin secretion; Type 2 diabetes mellitus.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

LinkOut - more resources