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Pancreatic GLP-1r binding potential is reduced in insulin-resistant pigs
Charles-Henri Malbert1, Alain Chauvin2, Michael Horowitz3
1Aniscan Unit, Department of Human Nutrition, INRAE, Saint-Gilles, France charles-henri.malbert@inrae.fr.
BMJ Open Diabetes Research & Care
|November 2, 2020
Summary
Reduced pancreatic glucagon-like peptide-1 receptor (GLP-1r) density and abdominal tissue perfusion contribute to the diminished insulinotropic effect of GLP-1 agonists in type 2 diabetes and obesity.
Area of Science:
- Endocrinology
- Metabolic Diseases
- Medical Imaging
Background:
- The insulinotropic effect of glucagon-like peptide-1 (GLP-1) is impaired in type 2 diabetes and obesity.
- Reduced pancreatic GLP-1 receptor (GLP-1r) density is hypothesized to underlie this diminished response in insulin-resistant obese individuals.
Purpose of the Study:
- To investigate the density of GLP-1 receptors (GLP-1r) in the pancreas of insulin-resistant obese pigs compared to lean controls.
- To assess the impact of hyperinsulinemia on GLP-1r density.
- To evaluate the role of tissue perfusion in GLP-1r agonist uptake.
Main Methods:
- Utilized positron emission tomography (PET) with a 68Ga-labeled GLP-1r agonist to measure GLP-1r density in lean and obese miniature pigs.
- Assessed the effect of induced hyperinsulinemia on GLP-1r density using sequential PET scans.
- Investigated tissue perfusion using 68Ga-DOTA imaging.
Main Results:
- Obese pigs exhibited a 75% reduction in pancreatic GLP-1r binding potential compared to lean pigs.
- Induced hyperinsulinemia in lean pigs significantly decreased pancreatic GLP-1r density.
- Reductions in GLP-1r ligand uptake correlated with decreased tissue perfusion.
Conclusions:
- Diminished insulinotropic effects of GLP-1 agonists in type 2 diabetes are attributed to reduced pancreatic GLP-1r density.
- Abdominal tissue hypoperfusion is a key factor contributing to the reduced efficacy of GLP-1 agonists.
- These findings highlight the interplay between receptor density and perfusion in metabolic regulation.
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