Vagal pathways for systemic regulation of glucose metabolism Author: Diba Borgmann1, Henning Fenselau2 Affiliation: <sup>1</sup> Synaptic Transmission in Energy Homeostasis Group, Max Planck Institute for Metabolism Research, Gleueler Strasse 50, 50931 Cologne, Germany; Center for Physical Activity Research (CFAS), Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark. <sup>2</sup> Synaptic Transmission in Energy Homeostasis Group, Max Planck Institute for Metabolism Research, Gleueler Strasse 50, 50931 Cologne, Germany; Center for Endocrinology, Diabetes and Preventive Medicine (CEDP), University Hospital Cologne, Kerpener Strasse 26, 50937 Cologne, Germany; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD), University of Cologne, Joseph-Stelzmann-Straße 26, Cologne 50931, Germany. Electronic address: henning.fenselau@sf.mpg.de. Conference/Journal: Semin Cell Dev Biol Date published: 2023 Jul 25 Other: Special Notes: doi: 10.1016/j.semcdb.2023.07.010. , Word Count: 205 Maintaining blood glucose at an appropriate physiological level requires precise coordination of multiple organs and tissues. The vagus nerve bidirectionally connects the central nervous system with peripheral organs crucial to glucose mobilization, nutrient storage, and food absorption, thereby presenting a key pathway for the central control of blood glucose levels. However, the precise mechanisms by which vagal populations that target discrete tissues participate in glucoregulation are much less clear. Here we review recent advances unraveling the cellular identity, neuroanatomical organization, and functional contributions of both vagal efferents and vagal afferents in the control of systemic glucose metabolism. We focus on their involvement in relaying glucoregulatory cues from the brain to peripheral tissues, particularly the pancreatic islet, and by sensing and transmitting incoming signals from ingested food to the brain. These recent findings - largely driven by advances in viral approaches, RNA sequencing, and cell-type selective manipulations and tracings - have begun to clarify the precise vagal neuron populations involved in the central coordination of glucose levels, and raise interesting new possibilities for the treatment of glucose metabolism disorders such as diabetes. Keywords: Cephalic phase; Glucose metabolism; Glucose tolerance; Insulin; Nodose ganglion; Pancreas; Parasympathetic nervous system; Vagal afferents; Vagal efferents; Vagus nerve. PMID: 37500301 DOI: 10.1016/j.semcdb.2023.07.010