1. Identification and characterization of GLP-1 receptor-expressing cells using a new transgenic mouse model
- Author
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Richards, Paul, Parker, Helen E., Adriaenssens, Alice E., Hodgson, Joshua M., Cork, Simon C., Trapp, Stefan, Gribble, Fiona M., and Reimann, Frank
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Gastrointestinal hormones -- Research -- Analysis -- Physiological aspects ,Health - 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. Diabetes 2014;63:1224-1233 | DOI: 10.2337/db13-1440, GLP-1 is one of several metabolically active peptides that are released from enteroendocrine cells in the gut epithelium after food intake. Together with glucose-dependent insulinotropic polypeptide (GIP), GLP-1 accounts for [...]
- Published
- 2014
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