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

Liu Yang, Xian-Tao Lei, Qi Huang, Ting Wang, Hong-Bin Sun, He-Yao Wang

Life sciences 2021 Mar 15

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The present study aimed to disclose a potent and selective GPR120 agonist LXT34 and its anti-diabetic effects. 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. 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. LXT34, a novel and potent GPR120-selective agonist, showed beneficial effects on improving glucose homeostasis in obesity-related type 2 diabetes. Copyright © 2021. Published by Elsevier Inc.

Citation

Liu Yang, Xian-Tao Lei, Qi Huang, Ting Wang, Hong-Bin Sun, He-Yao Wang. A novel GPR120-selective agonist promotes insulin secretion and improves chronic inflammation. Life sciences. 2021 Mar 15;269:119029