Pancreatic GLP-1r binding potential is reduced in insulin-resistant pigs
| Autor: | Malbert, Charles-Henri, Chauvin, Alain, Horowitz, Michael, Jones, Karen L |
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| Přispěvatelé: | US 1395 ANI-SCAN [INRA], Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Physiologie et Phénotypage des Porcs (UE 3P ), Center of Research Excellence in Translating Nutrition to Good Health, University of Adelaide |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
endocrine system
lcsh:RC648-665 Swine digestive oral and skin physiology [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism lcsh:Diseases of the endocrine glands. Clinical endocrinology glucagon-like peptide 1 Glucagon-Like Peptide-1 Receptor Diabetes Mellitus Type 2 insulin resistance Animals Insulin positron-emission tomography Pancreas Obesity Studies hormones hormone substitutes and hormone antagonists animal experimentation |
| Zdroj: | BMJ Open Diabetes Research & Care, Vol 8, Iss 2 (2020) BMJ Open Diabetes Research & Care BMJ Open Diabetes Research & Care, BMJ Journals, 2020, 8 (2), pp.e001540. ⟨10.1136/bmjdrc-2020-001540⟩ |
| ISSN: | 2052-4897 |
| Popis: | Introduction The insulinotropic capacity of exogenous glucagon like peptide-1 (GLP-1) is reduced in type 2 diabetes and the insulin-resistant obese. We have tested the hypothesis that this response is the consequence of a reduced pancreatic GLP-1 receptor (GLP-1r) density in insulin-resistant obese animals. Research design and methods GLP-1r density was measured in lean and insulin-resistant adult miniature pigs after the administration of a 68 Ga-labeled GLP-1r agonist. The effect of hyperinsulinemia on GLP-1r was assessed using sequential positron emission tomography (PET), both in the fasted state and during a clamp. The impact of tissue perfusion, which could account for changes in GLP-1r agonist uptake, was also investigated using 68 Ga-DOTA imaging. ResultsGLP-1r binding potential in the obese pancreas was reduced by 75% compared with lean animals. Similar reductions were evident for fat tissue, but not for the duodenum. In the lean group, induced hyperinsulinemia reduced pancreatic GLP-1r density to a level comparable with that of the obese group. The reduction in blood to tissue transfer of the GLP-1r ligand paralleled that of tissue perfusion estimated using 68 Ga-DOTA.ConclusionsThese observations establish that a reduction in abdominal tissue perfusion and a lower GLP-1r density account for the diminished insulinotropic effect of GLP-1 agonists in type 2 diabetes. |
| Databáze: | OpenAIRE |
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