Expression Profile of the GLP-1 Receptor in the Gastrointestinal Tract and Pancreas in Adult Female Mice

Abstract

Abstract Therapies based on glucagon-like peptide-1 receptor (GLP-1R) agonism are highly effective in treating type-2 diabetes and obesity, but the localization of GLP-1 receptors mediating the antidiabetic and other possible actions of GLP-1 is still debated. The purpose with this study was to identify sites of GLP-1R mRNA and protein expression in the mouse gastrointestinal system by means of GLP-1R antibody immunohistochemistry, Glp-1r mRNA fluorescence in situ hybridization (FISH) and 125I-exendin (9-39) autoradiography. As expected GLP-1R staining was observed in almost all β cells in the pancreatic islets, but more rarely in α and δ cells. In the stomach, GLP-1R staining was found exclusively in the gastric corpus mucous neck cells, known to protect the stomach mucosa. The Brunner’s glands were strongly stained for GLP-1R, and pretreatment with GLP-1 agonist exendin-4 caused internalization of the receptor and mucin secretion, while pretreatment with PBS or antagonist exendin (9–39) did not. In the intestinal mucosa, GLP-1R staining was observed in intraepithelial lymphocytes, lamina propria lymphocytes, and enteroendocrine cells containing secretin, peptide YY, and somatostatin, but not cholecystokinin. GLP-1R staining was seen in nerve fibers within the CHAT- and NO-positive myenteric plexuses from the gastric corpus to the distal large intestine being strongest in the mid- and hindgut area. Finally, intraperitoneal administration of radiolabeled exendin (9–39) strongly labeled myenteric fibers. In conclusion, this study expands our knowledge of GLP-1 receptor localization and suggests that GLP-1 may serve an important role in modulating gastrointestinal health and mucosal protection.