CarbohydratesGut-derived signaling molecules and vagal afferents in the control of glucose and energy homeostasisThorens, Bernarda; Larsen, Philip JustbAuthor Information aDepartment of Physiology and Department of Pharmacology and Toxicology, Lausanne, Switzerland; and bRheoscience, Copenhagen, Denmark Correspondence to Bernard Thorens, Department of Pharmacology and Toxicology, 27 Rue du Bugnon, CH-1005 Lausanne, Switzerland Tel: +41 21 692 53 90; fax: +41 21 692 53 55; e-mail: [email protected] Abbreviations GIP: glucose-dependent insulinatropic polypeptide GLP: glucagon-like peptide IGLE: interganglionic laminar ending IMA: intramuscular array MT: mucosal terminal NTS: nucleus of the tractus solitarius PPARα: peroxisome proliferator-activated receptor alpha PYY3-36: peptide YY3-36 VR-1: vanilloid receptor 1 Current Opinion in Clinical Nutrition and Metabolic Care: July 2004 - Volume 7 - Issue 4 - p 471-478 doi: 10.1097/01.mco.0000134368.91900.84 Buy Metrics Abstract Purpose of review The control of glucose and energy homeostasis, including feeding behaviour, is tightly regulated by gut-derived peptidic and nonpeptidic endocrine mediators, autonomic nervous signals, as well as nutrients such as glucose. We will review recent findings on the role of the gastrointestinal tract innervation and of portal vein glucose sensors; we will review selected data on the action of gastrointestinally released hormones. Recent findings The involvement of mechanosensory vagal afferents in postprandial meal termination has been clarified using mouse models with selective impairments of genes required for development of mechanosensory fibres. These activate central glucogen-like peptide-1/glucogen-like peptide-2 containing ascending pathways linking the visceroceptive brainstem neurons to hypothalamic nuclei. Mucosal terminals comprise the chemosensory vagal afferents responsive to postprandially released gastrointestinal hormones.The mechanism by which the hepatoportal glucose sensor stimulates glucose utilization by muscles was demonstrated, using genetically modified mice, to be insulin-independent but to require GLUT4 and AMP-kinase. This sensor is a key site of glucogen-like peptide-1 action and plays a critical role in triggering first phase insulin secretion. PeptideYY3-36 and ghrelin target intracerebral receptors as they are bidirectionally transported across the blood brain barrier. The anorectic functions of peripherally released peptideYY3-36 may however be mediated both via vagal afferents and intracerebral Y2 receptors in the brainstem and arcuate nucleus. Summary These recent findings demonstrate that the use of improved anatomical and physiological techniques and animal models with targeted gene modifications lead to an improved understanding of the complex role of gastrointestinal signals in the control of energy homeostasis. © 2004 Lippincott Williams & Wilkins, Inc.