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- Manell, Elin, et al.
(författare)
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Exploring the GLP-1-GLP-1R axis in porcine pancreas and gastrointestinal tract in vivo by ex vivo autoradiography
- 2021
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Ingår i: BMJ Open Diabetes Research & Care. - : BMJ Publishing Group Ltd. - 2052-4897. ; 9
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Tidskriftsartikel (refereegranskat)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 177Lu-exendin-4 in two groups of pigs, control or bottle-fed an oral glucose load. Positron emission tomography (PET) data from pigs injected with 68Ga-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 177Lu-exendin-4 was found in pancreas, and even higher uptake in areas of duodenum. Low uptake of 177Lu-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 68Ga-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.
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| 2. |
- Manell, Elin, et al.
(författare)
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Training Pigs for Oral Glucose Tolerance Test-Six Years' Experience of a Refined Model
- 2021
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Ingår i: Animals. - : MDPI AG. - 2076-2615. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Simple Summary Animal models for human diseases are used in situations where studies cannot be carried out on humans. While animal models in biomedical research play a pivotal part in the development of new and safe treatments for humans, it is important that the animals are used in the best way and that possible refinements are considered. Pigs are often used to model humans since the two species share many anatomical and physiological characteristics. This publication describes refinements in the training technique of pigs prior to an oral glucose tolerance test, a test commonly used in diabetes research where the individual drinks a certain amount of glucose followed by blood sampling. Sharing these results with the research community will help other researchers to successfully train pigs in such studies. Animal models of human diseases are important in biomedical research. When using animals for scientific purposes, the 3Rs (replace, reduce, refine) should be considered. Refinement of animal models is essential to ensure best use of animals, which is important for ethical reasons and to retrieve reliable research data. The present publication describes improvements to an oral glucose tolerance test (OGTT) model for pigs published in 2016. Historical data from 42 pigs were used to describe improvements in the training technique over six years. Pigs of various breeds and ages can be trained to bottle-feed glucose dissolved in water to undergo OGTT. This publication describes different tips and techniques to apply for successful training and will help researchers to minimize exclusions of pigs due to unsuccessful training. The improvements are an important contribution to the 3Rs.
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