title: DREADDing proglucagon neurons: a fresh look at metabolic regulation by the brain.
abstract: Glucagon-like peptide 1 receptor (GLP-1R) signaling in the CNS has been linked to reduced food intake, lower body weight, improved glucose homeostasis, and activation of CNS stress axes. GLP-1 is produced by cells that express proglucagon (GCG); however, the stimuli that activate GCG+ neurons are not well known, which has made understanding the role of this neuronal population in the CNS a challenge. In this issue of the JCI, Gaykema et al. use designer receptors exclusively activated by designer drugs (DREADD) technology to specifically activate GCG+ neurons in mouse models. While activation of GCG+ neurons did reduce food intake, and variably decreased hepatic glucose production, other GLP-1-associated effects were not observed - e.g., activation of stress axes or stimulation of insulin secretion - in response to GCG+ neuron activation. The authors have provided a valuable model to study this set of neurons in vivo, and their results provide new insights into the function of GCG+ neural activity in the brain and raise questions that will move research on this clinically relevant neural system forward.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Campbell
authors.forename: David A
authors.initials: DA
authors.lastname: D'Alessio
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D015195:Drug Design; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism; D006801:Humans; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D052336:Proglucagon / Q000494:pharmacology*; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D052336:Proglucagon; D000097789:Glucagon-Like Peptide-1 Receptor Agonists