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Exploring the GLP-1-GLP-1R axis in porcine pancreas and gastrointestinal tract in vivo by ex vivo autoradiography

Manell, Elin and Puuvuori, Emmi and Svensson, Anna and Velikyan, Irina and Hulsart-Billstrom, Gry and Hedenqvist, Patricia and Holst, Jens Juul and Jensen Waern, Marianne and Eriksson, Olof (2021). Exploring the GLP-1-GLP-1R axis in porcine pancreas and gastrointestinal tract in vivo by ex vivo autoradiography. BMJ Open Diabetes Research and Care. 9 :1 , e002083
[Research article]

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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 Lu-177-exendin-4 in two groups of pigs, control or bottle-fed an oral glucose load. Positron emission tomography (PET) data from pigs injected with Ga-68-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 Lu-177-exendin-4 was found in pancreas, and even higher uptake in areas of duodenum. Low uptake of Lu-177-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 Ga-68-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.

Authors/Creators:Manell, Elin and Puuvuori, Emmi and Svensson, Anna and Velikyan, Irina and Hulsart-Billstrom, Gry and Hedenqvist, Patricia and Holst, Jens Juul and Jensen Waern, Marianne and Eriksson, Olof
Title:Exploring the GLP-1-GLP-1R axis in porcine pancreas and gastrointestinal tract in vivo by ex vivo autoradiography
Series Name/Journal:BMJ Open Diabetes Research and Care
Year of publishing :2021
Volume:9
Number:1
Article number:e002083
Number of Pages:10
Publisher:BMJ PUBLISHING GROUP
Language:English
Publication Type:Research article
Article category:Scientific peer reviewed
Version:Published version
Copyright:Creative Commons: Attribution 4.0
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 3 Medical and Health Sciences > 302 Clinical Medicine > Endocrinology and Diabetes
Keywords:incretins, glucagon-like peptide 1, receptors, gastrointestinal hormone, glucose tolerance test
URN:NBN:urn:nbn:se:slu:epsilon-p-118776
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-p-118776
Additional ID:
Type of IDID
DOI10.1136/bmjdrc-2020-002083
Web of Science (WoS)000838754100002
ID Code:28836
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Dept. of Clinical Sciences
Deposited By: SLUpub Connector
Deposited On:13 Sep 2022 11:56
Metadata Last Modified:13 Sep 2022 12:01

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