Glucagon-Like-Peptide-1 Receptor Expression in Normal and Diseased Human Thyroid and Pancreas
Open accessAbstract
Glucagon-like-peptide-1 (GLP1) analogs may induce thyroid or pancreatic diseases in animals, raising questions about their use in diabetic patients. There is, however, controversy regarding expression of GLP1 receptors (GLP1R) in human normal and diseased thyroid and pancreas. Here, 221 human thyroid and pancreas samples were analyzed for GLP1R immunohistochemistry and compared with quantitative in vitro GLP1R autoradiography. Neither normal nor hyperplastic human thyroids containing parafollicular C cells express GLP1R with either method. Papillary thyroid cancer do not, and medullary thyroid carcinomas rarely express GLP1R. Insulin- and somatostatin-producing cells in the normal pancreas express a high density of GLP1R, whereas acinar cells express them in low amounts. Ductal epithelial cells do not express GLP1R. All benign insulinomas express high densities of GLP1R, whereas malignant insulinomas rarely express them. All ductal pancreatic carcinomas are GLP1R negative, whereas 6/20 PanIN 1/2 and 0/12 PanIN 3 express GLP1R. Therefore, normal thyroid, including normal and hyperplastic C cells, or papillary thyroid cancer are not targets for GLP1 analogs in humans. Conversely, all pancreatic insulin- and somatostatin-producing cells are physiological GLP1 targets, as well as most acini. As normal ductal epithelial cells or PanIN 3 or ductal pancreatic carcinomas do not express GLP1R, it seems unlikely that GLP1R is related to neoplastic transformation in pancreas. GLP1R-positive medullary thyroid carcinomas and all benign insulinomas are candidates for in vivo GLP1R targeting.
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When using validated antibodies, the GLP-1 receptor is only marginally expressed in thyroids of non-human primates and humans.
“When using validated antibodies, the GLP-1 receptor is only marginally expressed in thyroids of non-human primates and humans (78, 82).”
From Safety of Semaglutide (2021) · cites this paper as [82]
The Discussion (page not provided) says the study used a well-validated antibody and found no GLP-1 receptor expression in normal human thyroids, supporting the claim of little expression in humans. The paper does not establish the claim for non-human primates; its species comparison concerns rats and mice. (LLM, conf=0.86)
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- Authors
- Waser, B., Blank, A., Karamitopoulou, E., Perren, A., & Reubi, J. C.
- Affiliations
- University of Bern (CH)
- Corresponding author
- Reubi, Jean C
- Venue
- Modern Pathology
- Publisher
- Elsevier BV
- Published
- 2015-03
- Volume
- 28
- Issue
- 3
- Pages
- 391-402
- ISSN
- 0893-3952 (ISSN-L)
- OpenAlex
- W2033954313
- Cited by
- 119
- References
- 28
- Citations by year
- 2026: 9 · 2025: 18 · 2024: 11 · 2023: 14 · 2022: 5 · 2021: 8 · 2020: 10 · 2019: 11 · 2018: 6 · 2017: 11 · 2016: 5 · 2015: 8 · 2014: 3
- FWCI
- 7.24
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Modern Pathology (publishedVersion)
- PubMed (publishedVersion)
- BORIS (University Library Bern) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Keywords
- GLP-1 receptor, thyroid gland, pancreas, GLP-1 analogues, parafollicular C cells, thyroid hyperplasia, papillary thyroid carcinoma, medullary thyroid carcinoma, insulinoma, pancreatic islet cells, acinar cells, pancreatic intraepithelial neoplasia, pancreatic ductal carcinoma, oncogenic transformation
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Autoradiography, Humans, Immunohistochemistry, Pancreas, Pancreatic Neoplasms, Thyroid Diseases, Thyroid Gland, Thyroid Neoplasms, Blotting, Western, Receptors, Glucagon
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