Exploring the GLP-1-GLP-1R axis in porcine pancreas and gastrointestinal tract in vivo by ex vivo autoradiography
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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; Puuvuori, Emmi; Svensson, Anna; Velikyan, Irina; Hulsart-Billström, Gry; Hedenqvist, Patricia; Holst, Jens Juul; Jensen Waern, Marianne; Eriksson, Olof.
In: B M J Open Diabetes Research & Care, Vol. 9, e002083, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Exploring the GLP-1-GLP-1R axis in porcine pancreas and gastrointestinal tract in vivo by ex vivo autoradiography
AU - Manell, Elin
AU - Puuvuori, Emmi
AU - Svensson, Anna
AU - Velikyan, Irina
AU - Hulsart-Billström, Gry
AU - Hedenqvist, Patricia
AU - Holst, Jens Juul
AU - Jensen Waern, Marianne
AU - Eriksson, Olof
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
U2 - 10.1136/bmjdrc-2020-002083
DO - 10.1136/bmjdrc-2020-002083
M3 - Journal article
C2 - 33903116
VL - 9
JO - B M J Open Diabetes Research & Care
JF - B M J Open Diabetes Research & Care
SN - 2052-4897
M1 - e002083
ER -
ID: 260995253