Mechanism of acetate-sensitive G protein-coupled receptor-FFAR2 in regulating insulin secretion

LI Xiao-ran; XUE Yao-ming

doi:10.3969/j.issn.1674-4055.2017.03.11

Abstract：Objective To investigate the influence of acetate-sensitive G protein-coupled receptor (GPCR)-free fatty acid receptor 2 (FFAR2) its ligands on insulin secretion and relative mechanism.Methods The wild-type (WT) mice with C57BL/6J background (n=17) and Ffar2-knockout (KO) mice (n=15) were chosen, and the levels of weight, fasting blood glucose (FBG) and insulin level were detected on the 6th w and 26th w respectively. The islet cells were collected from mice, and divided randomly into groups. All groups were, respectively, given glucose in different doses and stimulation of FFAR2 ligands (SCA14, SCA15, CPTB and CMTB), and insulin secretion level was detected by using enzyme-linked immunosorbent assay (ELISA).Results The difference in weight, FBG and insulin level had no statistical significance in mice with different genotypes (allP>0.05). In the test of in vitro insulin secretion of pancreatic β cells, insulin secretion level stimulated by low-dose glucose had no difference in KO islet cells and WT islet cells, and that stimulated by high-dose glucose was lower in KO islet cells than that in WT islet cells (P<0.05). Acetate in the dose similar to physiological dose (1mM) stimulated insulin secretion. The insulin secretion level was 2 times more than that without acetate stimulation in WT islet cells, and this stimulating effect decreased in KO islet cells. SCA14 and SCA15 stimulated insulin secretion in WT islet cells, and had no similar effect in KO islet cells. CPTB and CMTB stimulated insulin secretion in both WT islet cells and KO islet cells.Conclusion The knockout of Ffar2 has no effect on mouse growing development. FFAR2 can regulate insulin secretion and has blood glucose dependency. Acetate, as a main ligand of FFAR2, can stimulate insulin secretion and has receptor dependency. Among other ligands of FFAR2, SCA14 and SCA15 have the similar effect as acetate, and CPTB and CMTB can inhibit insulin secretion and have no receptor dependency.