GLP-1: Molecular mechanisms and outcomes of a complex signaling system

Abstract

Meal ingestion provokes the release of hormones and transmitters, which in turn regulate energy homeostasis and feeding behavior. One such hormone, glucagon-like peptide-1 (GLP-1), has received significant attention in the treatment of obesity and diabetes due to its potent incretin effect. In addition to the peripheral actions of GLP-1, this hormone is able to alter behavior through the modulation of multiple neural circuits. Recent work that focused on elucidating the mechanisms and outcomes of GLP-1 neuromodulation led to the discovery of an impressive array of GLP-1 actions. Here, we summarize the many levels at which the GLP-1 signal adapts to different systems, with the goal being to provide a background against which to guide future research.

Keywords: Bariatric surgery; Feeding behavior; Glucagon-like peptide-1; Reward.

Figure 1.

GLP-1r mediated intracellular signaling via Gαs. Although GLP-1r is known to associate with multiple different G proteins, Gαs is the most well studied coupling. Here, the diversity of downstream signaling is shown through the differential actions of ERK 1/2 depending on its activation. Activation by PKA results in transient translocation to the nucleus, while activation by β arrestin results in the targeting of cytoplasmic partners.