Knockdown of GLP-1 Receptors in Vagal Afferents Affects Normal Food Intake and Glycemia. 2016

Jean-Philippe Krieger, and Myrtha Arnold, and Klaus G Pettersen, and Pius Lossel, and Wolfgang Langhans, and Shin J Lee
Physiology and Behavior Laboratory, Institute of Food, Nutrition, and Health, ETH Zurich, Zurich, Switzerland jean-philippe-krieger@ethz.ch.

Nutrient stimulation of enteroendocrine L cells induces the release of the incretin and satiating peptide glucagon-like peptide 1 (GLP-1). The vagus nerve innervates visceral organs and may contribute to the mediation of gut-derived GLP-1's effects on food intake, energy homeostasis, and glycemic control. To test the hypothesis that vagal afferent neuron (VAN) GLP-1 receptors (GLP-1Rs) are necessary for these effects of endogenous GLP-1, we established a novel bilateral nodose ganglia injection technique to deliver a lentiviral vector and to knock down VAN GLP-1Rs in male Sprague Dawley rats. We found that a full expression of VAN GLP-1Rs is not necessary for the maintenance of long-term energy balance in normal eating conditions. VAN GLP-1R knockdown (kd) did, however, increase meal size and accelerated gastric emptying. Moreover, postmeal glycemia was elevated and insulin release was blunted in GLP-1R kd rats, suggesting that VAN GLP-1Rs are physiological contributors to the neuroincretin effect after a meal. Collectively, our results highlight a crucial role for the VANs in mediating the effects of endogenous GLP-1 on food intake and glycemia and may promote the further development of GLP-1-based therapies.

UI MeSH Term Description Entries
D007328 Insulin A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1). Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D007422 Intestines The section of the alimentary canal from the STOMACH to the ANAL CANAL. It includes the LARGE INTESTINE and SMALL INTESTINE. Intestine
D008297 Male Males
D009475 Neurons, Afferent Neurons which conduct NERVE IMPULSES to the CENTRAL NERVOUS SYSTEM. Afferent Neurons,Afferent Neuron,Neuron, Afferent
D009620 Nodose Ganglion The inferior (caudal) ganglion of the vagus (10th cranial) nerve. The unipolar nodose ganglion cells are sensory cells with central projections to the medulla and peripheral processes traveling in various branches of the vagus nerve. Nodose Ganglia,Ganglia, Nodose,Ganglion, Nodose
D001786 Blood Glucose Glucose in blood. Blood Sugar,Glucose, Blood,Sugar, Blood
D004435 Eating The consumption of edible substances. Dietary Intake,Feed Intake,Food Intake,Macronutrient Intake,Micronutrient Intake,Nutrient Intake,Nutritional Intake,Ingestion,Dietary Intakes,Feed Intakes,Intake, Dietary,Intake, Feed,Intake, Food,Intake, Macronutrient,Intake, Micronutrient,Intake, Nutrient,Intake, Nutritional,Macronutrient Intakes,Micronutrient Intakes,Nutrient Intakes,Nutritional Intakes
D004734 Energy Metabolism The chemical reactions involved in the production and utilization of various forms of energy in cells. Bioenergetics,Energy Expenditure,Bioenergetic,Energy Expenditures,Energy Metabolisms,Expenditure, Energy,Expenditures, Energy,Metabolism, Energy,Metabolisms, Energy
D005746 Gastric Emptying The evacuation of food from the stomach into the duodenum. Emptying, Gastric,Emptyings, Gastric,Gastric Emptyings
D000067757 Glucagon-Like Peptide-1 Receptor A receptor for GLUCAGON-LIKE PEPTIDE 1 (GLP-1) expressed primarily on the surface of beta and ductal exocrine cells of the pancreas, as well as cells of other tissues. GLP-1 acts through GLP-1R to potentiate signaling in pancreatic cells in response to glucose-stimulated insulin secretion (GSIS). GLP-1 Receptor,GLP-1R Receptor,GLP1R Protein,GLP1R Receptor,GLP 1 Receptor,GLP 1R Receptor,Glucagon Like Peptide 1 Receptor,Peptide-1 Receptor, Glucagon-Like,Protein, GLP1R,Receptor, GLP-1,Receptor, GLP-1R,Receptor, GLP1R,Receptor, Glucagon-Like Peptide-1

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