Glucose-Sensing Mediated by Portal GLP-1 Receptor is Markedly Impaired in Insulin-Resistant Obese Animals.

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dc.contributor.authorMalbert, C.-H.
dc.contributor.authorChauvin, A.
dc.contributor.authorHorowitz, M.
dc.contributor.authorJones, K.L.
dc.date.issued2021
dc.description.abstractThe glucose portal sensor informs the brain of changes in glucose inflow through vagal afferents that require an activated glucagon-like peptide 1 receptor (GLP-1r). The GLP-1 system is known to be impaired in insulin-resistant conditions, and we sought to understand the consequences of GLP-1 resistance on glucose portal signaling. GLP-1–dependent portal glucose signaling was identified, in vivo, using a novel ⁶⁸Ga-labeled GLP-1r positron-emitting probe that supplied a quantitative in situ tridimensional representation of the portal sensor with specific reference to the receptor density expressed in binding potential units. It also served as amap for single-neuron electrophysiology driven by an image-based abdominal navigation. We determined that in insulin-resistant animals, portal vagal afferents failed to inhibit their spiking activity during glucose infusion, a GLP-1r–dependent function. This reflected a reduction in portal GLP-1r binding potential, particularly between the splenic vein and the entrance of the liver.We propose that insulin resistance, through a reduction in GLP-1r density, leads to functional portal desensitization with a consequent suppression of vagal sensitivity to portal glucose.
dc.description.statementofresponsibilityCharles-Henri Malbert, Alain Chauvin, Michael Horowitz, and Karen L. Jones
dc.identifier.citationDiabetes, 2021; 70(1):99-110
dc.identifier.doi10.2337/db20-0361
dc.identifier.issn0012-1797
dc.identifier.issn1939-327X
dc.identifier.orcidMalbert, C.-H. [0000-0002-0665-4545]
dc.identifier.orcidHorowitz, M. [0000-0002-0942-0306]
dc.identifier.orcidJones, K.L. [0000-0002-1155-5816]
dc.identifier.urihttps://hdl.handle.net/2440/145906
dc.language.isoen
dc.publisherAmerican Diabetes Association
dc.rights© 2020 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www.diabetesjournals .org/content/license.
dc.source.urihttps://doi.org/10.2337/db20-0361
dc.subjectglucose portal sensor; brain; glucose inflow; glucagon-like peptide 1 receptor (GLP-1r); single-neuron electrophysiology; insulin-resistant
dc.subject.meshPortal Vein
dc.subject.meshAnimals
dc.subject.meshSwine
dc.subject.meshSwine, Miniature
dc.subject.meshInsulin Resistance
dc.subject.meshObesity
dc.subject.meshInsulin
dc.subject.meshGlucose
dc.subject.meshPositron-Emission Tomography
dc.subject.meshBody Composition
dc.subject.meshGlucagon-Like Peptide-1 Receptor
dc.subject.meshInsulin Secretion
dc.titleGlucose-Sensing Mediated by Portal GLP-1 Receptor is Markedly Impaired in Insulin-Resistant Obese Animals.
dc.typeJournal article
pubs.publication-statusPublished

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