Determination of the effect of liraglutide on expression of GPCR genes associated with insulin secretion and beta cell expression in mouse pancreatic beta cells

Diabetes is an important public health problem due to its increasing frequency and disease burden. Liraglutide is a long-acting glucagon-like peptide drug with antihyperglycemic activity. This drug acts by binding to the Glucagon-Like Peptide- 1 Receptor (GLP-1R) in the cell membrane. G protein-coupled receptors (GPCR) are molecules that mediate important signaling pathways on the cell surface. Studies investigating the insulin secretory potential for certain G protein-coupled receptors in pancreatic beta cells have proven the role of GPCRs in the regulation of pancreatic beta cell function. In our thesis study, the changes in gene expression of GPR75, GPR56, GLP1R, M3R, CB1R genes, which are GPCRs, in response to liraglutide treatment in non-obese diabetic NIT-1 mouse pancreatic beta cells were investigated. NIT-1 mouse pancreatic beta cells were treated with liraglutide at concentrations of 10, 100, 1000 nM for 30, 60, 120, 240 minutes. Gene expression changes at the mRNA level of GPCR genes (GPR75, GPR56, GLP1R, M3R, CB1R) were determined by qPCR method. A significant change in GLP1-R receptor protein was detected for all times tested in response to liraglutide treatment at 1000 nM concentration in vitro. Because 240 minutes liraglutide treatment adversely affected NIT-1 cell growth, no useful data were obtained from these groups. It is observed that GPR75, GPR56, M3R, CB1R mRNA levels decreased slightly at minute 30, increased statistically at minute 60, and decreased again at minute 120. Although liraglutide administration appears to have a transient effect on the expression of investigated genes in NIT-1 mouse pancreatic beta cells, it is thought that the GPR75, GPR56, M3R and CB1R genes may mediate the effects of liraglutide on beta cells. Changes in the expression of GPR75, GPR56, M3R and CB1R genes support that these genes and their products may be target molecules for anti-diabetic and anti-obesity therapy. Key words: Diabetes Mellitus, GPCR, Insulin Secretion, Liraglutide