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- Title
DREADDing proglucagon neurons: a fresh look at metabolic regulation by the brain.
- Authors
Campbell, Jonathan E.; D'Alessio, David A.
- 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.
- Subjects
NEURONS; GLUCAGON-like peptide-1 receptor; CENTRAL nervous system; LABORATORY mice; DRUG design; BRAIN metabolism; ANIMALS; MICE; DRUG development; PROGLUCAGON
- Publication
Journal of Clinical Investigation, 2017, Vol 127, Issue 3, p793
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI92845