Neuronal and intracellular signaling pathways mediating GLP-1 energy balance and glycemic effects

The glucagon-like peptide-1 (GLP-1) system is physiologically involved in the control of energy balance and blood glucose homeostasis. Thus, GLP-1-based pharmaceuticals are emerging as a potent treatment for not only type II diabetes mellitus (T2DM), but potentially for obesity as well. Despite the plethora of investigations over the last two decades examining the physiological, endocrine, and behavioral responses mediated by the GLP-1 receptor (GLP-1R), the field is only recently embracing the perspective that GLP-1-mediated control of food intake and glycemia involves action on GLP-1R that are distributed throughout the periphery (e.g. pancreatic β-cells, vagus nerve), as well as action on many GLP-1R-expressing nuclei within the central nervous system (CNS). This review highlights peripheral, as well as central GLP-1R populations that mediate GLP-1's food intake inhibitory and glycemic effects. In addition, focus is devoted to recent studies that examine the GLP-1R-mediated intracellular signaling pathways that are required for GLP-1's glycemic and feeding responses.