Objectives: Studies have proposed pro-oncogenic effects of glucagon-like peptide-1 receptor (GLP-1R) agonists in the pancreas by promoting GLP-1R overactivation in pancreatic cells. However, the expression of GLP-1R in normal and neoplastic pancreatic cells remains poorly defined, and reliable methods for detecting GLP-1R in tissue specimens are needed.
Methods: We used RNA in situ hybridization to quantify glp-1r RNA in surgically resected human pancreatic specimens, including pancreatic ductal adenocarcinoma (PDAC), preinvasive intraepithelial lesions (pancreatic intraepithelial neoplasia), and non-neoplastic ductal, acinar, and endocrine cells. A mixed-effect linear regression model was used to investigate the relationship between glp-1r signals and all cells, ordered by increasing grade of dysplasia.
Results: All cell types had evidence of glp-1r transcripts, with the highest expression in endocrine cells and lowest in ductal cells. The slope of the fitted line was not significantly different from zero (0.07; 95% confidence interval, -0.0094 to 0.244; P = 0.39), suggesting that progression from normal cells to PDAC is not associated with a parallel increase in glp-1r RNA. A series of pairwise comparisons between all cell types with respect to their glp-1r expression showed no significant difference in glp-1r in cancer, pancreatic intraepithelial neoplasia, and acinar and ductal cells.
Conclusions: Our study supports the lack of evidence for GLP-1R overexpression in PDAC.