Identification and Characterization of GLP-1 Receptor–Expressing Cells Using a New Transgenic Mouse Model

  1. Frank Reimann1
  1. 1Cambridge Institute for Medical Research and Medical Research Council Metabolic Diseases Unit, Addenbrooke’s Hospital, Cambridge, U.K.
  2. 2Department of Neuroscience, Physiology and Pharmacology, University College London, London, U.K.
  1. Corresponding author: Fiona M. Gribble, fmg23{at}cam.ac.uk.

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.

Footnotes

  • Received September 19, 2013.
  • Accepted November 21, 2013.

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  1. Diabetes vol. 63 no. 4 1224-1233
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