title: Identification and characterization of GLP-1 receptor-expressing cells using a new transgenic mouse model.
abstract: GLP-1 is an intestinal hormone with widespread actions on metabolism. Therapies based on GLP-1 are highly effective because they increase glucose-dependent insulin secretion in people with type 2 diabetes, but many reports suggest that GLP-1 has additional beneficial or, in some cases, potentially dangerous actions on other tissues, including the heart, vasculature, exocrine pancreas, liver, and central nervous system. Identifying which tissues express the GLP-1 receptor (GLP1R) is critical for the development of GLP-1-based therapies. Our objective was to use a method independent of GLP1R antibodies to identify and characterize the targets of GLP-1 in mice. Using newly generated glp1r-Cre mice crossed with fluorescent reporter strains, we show that major sites of glp1r expression include pancreatic β- and δ-cells, vascular smooth muscle, cardiac atrium, gastric antrum/pylorus, enteric neurones, and vagal and dorsal root ganglia. In the central nervous system, glp1r-fluorescent cells were abundant in the area postrema, arcuate nucleus, paraventricular nucleus, and ventromedial hypothalamus. Sporadic glp1r-fluorescent cells were found in pancreatic ducts. No glp1r-fluorescence was observed in ventricular cardiomyocytes. Enteric and vagal neurons positive for glp1r were activated by GLP-1 and may contribute to intestinal and central responses to locally released GLP-1, such as regulation of intestinal secretomotor activity and appetite.
authors.affiliation: Cambridge Institute for Medical Research and Medical Research Council Metabolic Diseases Unit, Addenbrooke's Hospital, Cambridge, U.K.
authors.forename: Paul
authors.initials: P
authors.lastname: Richards
authors.forename: Helen E
authors.initials: HE
authors.lastname: Parker
authors.forename: Alice E
authors.initials: AE
authors.lastname: Adriaenssens
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Hodgson
authors.forename: Simon C
authors.initials: SC
authors.lastname: Cork
authors.forename: Stefan
authors.initials: S
authors.lastname: Trapp
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Gribble
authors.forename: Frank
authors.initials: F
authors.lastname: Reimann
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000166:cytology / Q000378:metabolism; D000067757:Glucagon-Like Peptide-1 Receptor; D006325:Heart Atria / Q000166:cytology / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D018027:Receptors, Glucagon / Q000096:biosynthesis*
chemical_list: C000593834:Glp1r protein, mouse; D000067757:Glucagon-Like Peptide-1 Receptor; D018027:Receptors, Glucagon