title: Vagal mediation of GLP-1's effects on food intake and glycemia.
abstract: Nutrient stimulation of the enteroendocrine L-cells induces the release of the glucagon-like peptide-1 (GLP-1), an incretin and satiating peptide. Due to its short half-life, meal-induced GLP-1's effects on food intake and glycemia are likely to be mediated in part by a paracrine signaling mechanism near the site of release. Early and recent findings from vagus nerve lesion studies scrutinized in this review strongly support an important role of the vagus nerve in mediating GLP-1's effects. Peripheral GLP-1 or GLP-1R agonist treatment failed to elicit the full satiating effects and maintain glucose homeostasis in various lesion models. The potential mechanisms underlying the vagal GLP-1R mediated satiation and glycemic control presumably involve the activation of caudal brainstem neurons via glutamatergic signaling, which activate a vagal reflex loop or/and relay the information to higher brain centers. Recent studies also presented here, however, diminish the relevance of the vagus nerve for the pharmacological intervention of obesity and diabetes with chronic GLP-1R agonist treatments, suggesting that endogenous intestinal GLP-1 and GLP-1R agonists may activate different GLP-1R populations. Finally, lesion-based approaches are limited and new technical approaches are discussed to improve the understanding of vagal GLP-1R functions in maintaining normal energy balance and its relevance in pharmacological interventions.
authors.affiliation: Physiology and Behavior Laboratory, Institute of Food, Nutrition, and Health, ETH Zurich, Switzerland. Electronic address: jean-philippe-krieger@ethz.ch.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Krieger
authors.affiliation: Physiology and Behavior Laboratory, Institute of Food, Nutrition, and Health, ETH Zurich, Switzerland.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Langhans
authors.affiliation: Physiology and Behavior Laboratory, Institute of Food, Nutrition, and Health, ETH Zurich, Switzerland.
authors.forename: Shin J
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D004435:Eating / Q000502:physiology*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D014630:Vagus Nerve / Q000378:metabolism*
chemical_list: D000067757:Glucagon-Like Peptide-1 Receptor; D052216:Glucagon-Like Peptide 1; D005947:Glucose