Supplemental_material_R1__with_supp_fig.pdf (1.63 MB)
Download fileGlucose-sensing mediated by portal GLP-1 receptor is markedly impaired in insulin-resistant obese animals
figure
posted on 2020-10-16, 21:55 authored by Ada AdminAda Admin, Charles-Henri Malbert, Alain Chauvin, Michael Horowitz, Karen L JonesThe glucose portal sensor informs the brain of changes
in glucose inflow via vagal afferents that require an activated GLP-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 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.