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

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.

Duke Scholars

Author Jonathan Edward Campbell Medicine, Endocrinology, Metabolism, and Nutrition

Author David A D'Alessio Medicine, Endocrinology, Metabolism, and Nutrition