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Glucose sensing mediated by portal Glucagon-Like Peptide 1 receptor Is markedly Impaired in insulin-resistant obese animals

Abstract : The 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 Ga-68-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 a map 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.
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https://hal.inrae.fr/hal-03101284
Contributor : Emilie Bernard <>
Submitted on : Thursday, January 7, 2021 - 9:04:15 AM
Last modification on : Tuesday, May 11, 2021 - 3:11:04 PM

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Charles-Henri Malbert, Alain Chauvin, Michael Horowitz, Karen Jones. Glucose sensing mediated by portal Glucagon-Like Peptide 1 receptor Is markedly Impaired in insulin-resistant obese animals. Diabetes, American Diabetes Association, 2020, 70 (1), pp.99-110. ⟨10.2337/db20-0361⟩. ⟨hal-03101284⟩

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