Tissue Distribution Of Free Fatty Acid Receptors And The Effect Of Gpr40’s Ligands On Insulin Secretion In Pancreatic β Cells

BackgroundThe G protein-coupled receptors are a superfamily of cell membrane receptors, theyare activated by a variety of endogenous ligands such as amines, fatty acids, aminoacids, peptides, proteins, steroids. A family of G-protein-coupled receptors has beenidentified that exhibits high affinity for fatty acids, such as GPR40、GPR41、GPR43、GPR84、GPR119、GPR120, and they are callded free fatty acid receptors (FFARs).TheseFFARs are proposed to play critical roles in diabetes mellitus.AimGPR40is a membrane-bound receptor paired with medium and long-chain fatty acidsas endogenous ligands. However, the role of GPR40in the short-term effects of fattyacids on insulin secretion remains controversial. This study aimed to test the hypothesisthat GPR40plays a role in insulin secretion after being combined with its endogenousligands linoleic acid(LA)、agonist GW9508and antagonist GW1100.Material and methodsThe primary islets cell were prepared by enzymatic digestion and gradient separationfrom the pancreas of rat. Islet cell purity and viability were determined by dithizone andtrypan blue staining. Expression changes in various organs of rats and the islet cells byRT-PCR method for detection of mRNA. The insulin levels were detemined by ELISA. ResultsRT-PCR results showed that: GPR40was predominantly expressed in the brain、heart、spleen and colon tissue. In addition, we found that GPR41was highly expressedin every tissues except liver, GPR43was expressed only in the spleen and colon,GPR119was expressed abundantly in the brain and kidney, GPR120was expressedhighest in the colon; The estimated mRNA copy number of the GPR40gene in isolatedislets was higher than other genes encoding receptors for FFA; GW9508and LA dosedependently potentiated glucose-stimulated insulin secretion in primary islet cells andINS-1; GW1100inhibited GPR40elevations stimulated by its agonist (*p<0.05,**p<0.01; n=3))ConclusionsGPR40physiological functions is closely related to its tissue distribution, GPR40play an important role in regulating insulin secretion form pancreaticβcells. We believethat its agonist GW9508is expected to become new drugs for the treatment of diabetes.