Proposed glial-neuronal loop at work in central sensing of hypoglycemia via GLUT2, based on the study by Marty et al. in this issue (9). This scheme illustrates the pivotal role of GLUT2 in glial cells in first-hand detection of hypoglycemia. How these specific glial cells then connect to neurons within the brainstem (likely in the NTS and the dorsal motor nucleus of the vagus) to relay information is unknown but may involve the lactate shuttle as well as signaling via the Kir6.2 ATP-regulated K⁺ channel (not illustrated). The drop in glycemia may also be directly sensed by neurons and pancreatic α and β cells but not through GLUT2 (the transporter/detectors involved are so far unknown). Ultimately, autonomic nervous signals and the drop in intraislet insulin levels promote glucagon secretion.