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

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

Histology & Inflammation (DT,JR) and Diabetes Biology and 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)

Correspondence to: R. Scott Heller, Department of Developmental Biology, Hagedorn Research Institute, Niels Steensensvej 6, DK2820 Gentofte, Denmark. E-mail: shll{at}hagedorn.dk

We studied the intra-islet localization of the glucagon-like peptide 1 receptor (GLP-1R) by colocalization studies of the GLP-1R mRNA and protein with islet cell hormones in mice, rats, and humans. In contrast to previous reports, we show that the GLP-1R is selectively located on the β cells. The localization of GLP-1R in islets and ducts was studied using ISH and double and triple fluorescence microscopy. In normal pancreatic tissue from mice and rats, GLP-1R mRNA was only detectable in the β 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 colocalized 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 β cells and the lack of receptor immunoreactivity on cells cannot 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. (J Histochem Cytochem 56:841–851, 2008)

Key Words: glucagon like peptide 1 receptor • ISH • insulin • somatostatin • glucagon • immunohistochemistry

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