DREADDing proglucagon neurons: a fresh look at metabolic regulation by the brain

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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

Jonathan E. Campbell, David A. D’Alessio