Glucose Sensing Mediated by Portal Glucagon-Like Peptide 1 Receptor Is Markedly Impaired in Insulin-Resistant Obese Animals
- 16 October 2020
- journal article
- research article
- Published by American Diabetes Association in Diabetes
- Vol. 70 (1), 99-110
- https://doi.org/10.2337/db20-0361
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 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.Keywords
Funding Information
- Bpi France
This publication has 68 references indexed in Scilit:
- Vagal Blocking Improves Glycemic Control and Elevated Blood Pressure in Obese Subjects with Type 2 Diabetes MellitusJournal of Obesity, 2013
- Impairment of GLP1‐induced insulin secretion: role of genetic background, insulin resistance and hyperglycaemiaDiabetes, Obesity and Metabolism, 2012
- PET imaging for receptor occupancy: meditations on calculation and simplificationJournal of Biomedical Research, 2012
- Glucose sensing and the pathogenesis of obesity and type 2 diabetesInternational Journal of Obesity, 2008
- The Integrative Role of CNS Fuel-Sensing Mechanisms in Energy Balance and Glucose RegulationAnnual Review of Physiology, 2008
- Consensus Nomenclature for in vivo Imaging of Reversibly Binding RadioligandsJournal of Cerebral Blood Flow & Metabolism, 2007
- Role Played by Vagal Chemical Sensors in the Hepato-portal Region and Duodeno-intestinal Canal: An Electrophysiological StudyChemical Senses, 2005
- Sensory nerves contribute to insulin secretion by glucagon-like peptide-1 in miceAmerican Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2004
- Electric field stimulation of excitable tissueIEEE Engineering in Medicine and Biology Magazine, 1998
- Portal venous and segmental anatomy of the right hemiliver: observations based on three-dimensional spiral CT renderings.American Journal of Roentgenology, 1994