Expression of the GLP-1 Receptor in Mouse, Rat, and Human Pancreas

Ditte Tornehave ¹, Peter Kristensen ¹, John Rømer ¹, Lotte Bjerre Knudsen ¹ and R. Scott Heller ^1*

¹ Histology & Inflammation (DT,JR) and Diabetes Biology & Pharmacology Management (LBK), Novo Nordisk A/S, Måløv, Denmark; Global Development Management, Novo Nordisk A/S, Bagsvaerd, Denmark (PK); and Development Biology, Hagedorn Research Institute, Novo Nordisk A/S, Gentofte, Denmark (RSH)

^* To whom correspondence should be addressed. E-mail: shll{at}hagedorn.dk.

Submitted on March 5, 2008
Accepted on 22 May 2008

	Abstract

We have investigated the intra-islet localization of the glucagon-like peptide 1 receptor (GLP-1R) by co-localization studies of the GLP-1R mRNA and protein with islet cell hormones in mice, rats and humans. In contrast to previous reports we here demonstrate that the GLP-1R is selectively located on the -cells. The localization of GLP-1R in islets and ducts was studied using in situ hybridization and double and triple fluorescence microscopy. In normal pancreatic tissue from mice and rat GLP-1R mRNA was only detectable in the -cells. Double and triple immunofluorescence using two different GLP-1R antisera and combinations of insulin, glucagon, pancreatic polypeptide and somatostatin showed that GLP-1R protein is almost exclusively co-localized with insulin. The same pattern was observed in human pancreas but the GLP-1R expression was more heterogeneous, with populations of insulin immunoreactive cells with high and low expression. This is the first time that the GLP-1R has been localized in human islets. Furthermore, GLP-1R immunoreactivity was found in the pancreatic ducts in mouse, rat and human pancreas. As an important confirmation of the specificity of our methods we found no signals for GLP-1R mRNA or protein in pancreatic tissue from gene-targeted GLP-1R deficient mice. In conclusion, our data suggest that the GLP-1 receptor is restricted to the pancreatic -cells and the lack of receptor immunoreactivity on -cells can not be explained suitably to correspond with published in vivo and in vitro data. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials.

Key Words: glucagon like peptide 1, GLP-1, receptor, in situ hybridization, insulin, somatostatin, glucagon, immunohistochemistry

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