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

作者:Campbell Jonathan E; D'Alessio David A*
来源:Journal of Clinical Investigation, 2017, 127(3): 793-795.
DOI:10.1172/JCI92845

摘要

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.

  • 出版日期2017-3-1