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• W3158367088 abstract "Introduction Glucagon-like peptide-1 (GLP-1) increases insulin secretion from pancreatic beta-cells and GLP-1 receptor (GLP-1R) agonists are widely used as treatment for type 2 diabetes mellitus. Studying occupancy of the GLP-1R in various tissues is challenging due to lack of quantitative, repeatable assessments of GLP-1R density. The present study aimed to describe the quantitative distribution of GLP-1Rs and occupancy by endogenous GLP-1 during oral glucose tolerance test (OGTT) in pigs, a species that is used in biomedical research to model humans. Research design and methods GLP-1R distribution and occupancy were measured in pancreas and gastrointestinal tract by ex vivo autoradiography using the GLP-1R-specific radioligand 177 Lu-exendin-4 in two groups of pigs, control or bottle-fed an oral glucose load. Positron emission tomography (PET) data from pigs injected with 68 Ga-exendin-4 in a previous study were used to retrieve data on biodistribution of GLP-1R in the gastrointestinal tract. Results High homogenous uptake of 177 Lu-exendin-4 was found in pancreas, and even higher uptake in areas of duodenum. Low uptake of 177 Lu-exendin-4 was found in stomach, jejunum, ileum and colon. During OGTT, there was no increase in plasma GLP-1 concentrations and occupancy of GLP-1Rs was low. The ex vivo autoradiography results were highly consistent with to the biodistribution of 68 Ga-exendin-4 in pigs scanned by PET. Conclusion We identified areas with similarities as well as important differences regarding GLP-1R distribution and occupancy in pigs compared with humans. First, there was strong ligand binding in the exocrine pancreas in islets. Second, GLP-1 secretion during OGTT is minimal and GLP-1 might not be an important incretin in pigs under physiological conditions. These findings offer new insights on the relevance of porcine diabetes models." @default.
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• W3158367088 date "2021-04-01" @default.
• W3158367088 modified "2023-09-27" @default.
• W3158367088 title "Exploring the GLP-1–GLP-1R axis in porcine pancreas and gastrointestinal tract in vivo by ex vivo autoradiography" @default.
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• W3158367088 doi "https://doi.org/10.1136/bmjdrc-2020-002083" @default.
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