The Function And Mechanism Of GPR120 In Pancreatic Islets ? Cells

Diabetes is a chronic non-communicable disease that threatens our health.It is divided into type 1 diabetes mellitus(T1DM)and type 2 diabetes mellitus(T2DM).Type 2 diabetes is often caused by poor eating habits and lifestyles.Patients exhibit reduced insulin sensitivity,high blood glucose levels,and multiple complications such as cataracts,cardiovascular and cerebrovascular diseases,and kidney disease.And so on,these diseases seriously affect the normal life and quality of life of patients.Therefore,it is very important to find scientific and effective methods to treat diabetes.G protein-coupled receptor 120(GPR120),also known as free fatty acid receptor 4(FFA4),is an unsaturated fatty acid receptor that belongs to the rhodopsin-like receptor family in G protein-coupled receptor superfamily.GPR120 plays an important role in regulating the secretion of insulin and is considered as a potential drug target for the treatment of diabetes.Studies have shown that GPR120 can regulate gastrointestinal peptide secretion,taste preference and glucose homeostasis after activation,thereby regulating energy metabolism and triggering anti-inflamma-tory effects.In primary adipocytes and 3T3-L1 adipocyte cell lines,GPR120 is activated to facilitate translocation of the glucose transporter GLUT4 to the plasma membrane,resulting in increased glucose transport.In 2010,Da Young Oh of the University of California,USA constructed the GPR1 20-deficient mouse model.Defect mice showed more sensitivity to high-fat diets,resulting in glucose intolerance,insulin resistance,and decreased differentiation of fatty liver and adipocytes.Insulin is an important hormone that balances blood sugar in the human body.It is secreted by pancreatic beta cells.Islet cells are composed of a variety of cells,including insulin-producing beta cells,alpha cells that release glucagon,delta cells that secrete somatostatin,gamma cells that release ghrelin and pancreatic polypeptide(PP)producing cells.The activation of GPR120 in pancreatic islet beta cells can promote the secretion of insulin.A recent paper reported that after GPR120 was activated in islets,somatostatin secreted by islet delta cells was inhibited.These findings suggest that GPR120 also plays an important role in islet delta cells and may be an important molecule in the regulation of islet loops.However,the specific role and mechanism of GPR120 in pancreatic islet delta cells have not yet been clarified and needs to be resolved.Therefore,this article mainly studies the regulation of somatostatm synthesis and secretion and its mechanism in pancreatic islet delta cells.Research purposesTo explore the regulation of somatostatin synthesis and secretion by GPR120 in pancreatic islet delta cells and its mechanism.Research methods1.RT-PCR and q-RT-PCR were performed to detect expression levels of GPR 120 in various tissues and cells.2.ELISA was used to detect the stimulation of islet delta cells with high glucose/high glucose+GPR 120 and the level of somatostatin secretion.3.RT-PCR and q-RT-PCR were used to detect the changes of somatostatin synthesis at different time points in pancreatic islet ? cells that were treated with GPR 120 agonists or without GPR 120 agonists under high glucose conditions.4.Islet delta cells are stimulated by PKC blockers/L-type calcium channels/R-type calcium channel blockers to detect the secretion of somatostatin by ELISA.5.First,the interfering efficiency of ?-arrestin1/?-arrestin2 in pancreatic islet ?cells was detected by Western blot.Then,the cells were stimulated with glucose/high glucose+GPR120 and the level of somatostatin secretion was detected by ELISA.6.BRET was used to detect the ability of GPR120 to recruit ?-arrestin1 in HEK293 cells.7.Confocal was used to detect the colocalization of GPR120 with ?-arrestin1 in 293 cell line and TGP52 cell line(islet delta cell line).8.RT-PCR and q-RT-PCR were performed to detect mRNA levels of G protein-coupled receptor kinase family(GRK1-7)in various tissues and cells.9.GRK5 expression was inhibited in TGP52 cells,and the co-localization of GPR120-YFP and ?-arrestinl-RFP was affected.Results1.GPR120 and GRK1-7 are widely expressed in various tissues and cells.In islet delta cells,GPR120 has the highest expression level.2.While high glucose promote can the secretion of somatostatin in islet delta cells,incubating with GPR120 agonist GW9508 could suppress this promotion.However,interfering with ?-arrestin1 can release the inhibitory effect on somatostatin secretion in ? cell lines that caused by GW9508 incubation.3.Islet ? cells were cultured in high glucose conditions and incubated for different time points with GPR120 agonists,somatostatin synthesis was inhibited.4.The GPR120-YFP and ?-arrestin1-RFP plasmids were co-transfected in 293 cells/TGP52 cells and their colocalization was observed.5.When GRK5 was inhibited in TGP52 cells,the colocalization of GPR120-YFP and ?-arrestin1-RFP was affected.ConclusionActivation of GPR120 in pancreatic islet delta cells can inhibit the synthesis and secretion of somatostatin caused by high glucose,which is regulated by the GRK5/?-arrestin 1 signaling pathway.