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Identification and characterization of GLP-1 receptor-expressing cells using a new transgenic mouse model.


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Type

Article

Change log

Authors

Richards, Paul 
Parker, Helen E 
Adriaenssens, Alice E 
Hodgson, Joshua M 
Cork, Simon C 

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.

Description

Keywords

Animals, Central Nervous System, Glucagon-Like Peptide-1 Receptor, Heart Atria, Islets of Langerhans, Mice, Mice, Transgenic, Muscle, Smooth, Vascular, Receptors, Glucagon

Journal Title

Diabetes

Conference Name

Journal ISSN

0012-1797
1939-327X

Volume Title

Publisher

American Diabetes Association

Rights

DSpace@Cambridge license
Sponsorship
Medical Research Council (MC_UU_12012/3)
Medical Research Council (MC_UU_12012/5)
Wellcome Trust (084210/Z/07/Z)
Wellcome Trust (088357/Z/09/A)
Wellcome Trust (088357/Z/09/Z)
Medical Research Council (MC_PC_12012)
This research was funded by Wellcome Trust grants to FMG and FR (WT088357/Z/09/Z and WT084210/Z/07/Z), Wellcome Trust PhD studentships to PR and AEA and the MRC Metabolic Diseases Unit (MDU), Cambridge. GLP-1 immuno-assays were performed by Keith Burling at the MRC-MDU. iCre was a kind gift from Rolf Sprengel, Heidelberg, Germany. FMG and FR are joint guarantors of this manuscript. No authors have any conflicts of interest.