Identification and characterisation of glucagon-like peptide-1 receptor expressing cells using a new transgenic mouse model

  1. Frank Reimann,1
  1. 1Cambridge Institute for Medical Research and MRC Metabolic Diseases Unit, Addenbrooke’s Hospital, Hills Road, Cambridge, CB2 0XY, UK
  2. 2Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6BT, UK
  1. Corresponding author: Fiona M Gribble Email: fmg23{at}cam.ac.uk

Abstract

Glucagon-like peptide-1 (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 identify and characterise the targets of GLP-1 in mice, using a method independent of GLP1R antibodies. 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 sytem, 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. Glp1r-positive enteric and vagal neurons 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

  • * Joint first authors

  • Joint senior authors

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

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