Abnormal feeding initiation and termination after fasting periods due to a failure in the glucosensing mechanism has been reported for GLUT2-knockout mice subjected to fasting/feeding cycles28. GLUT2-dependent sensors regulate glucagon secretion under glucoprivic conditions41. Thus, GLUT2 and GK expression in tanycytes may have important physiological consequences. A high Km for glucose transport and the presence of GK suggest that tanycytes may increase glucose uptake and metabolization rates proportionally to changes in blood glucose levels18. In this regard, GLUT2 is the only glucose transporter with a high Km that has been probed identified to have a role in glucosensing. Among the four known hexokinase isoforms, GK is the only one with a Km in the order of millimolar, which is necessary for participating in the glucosensing mechanism. It is interesting to note the possibility that different populations of tanycytes could detect glucose differently. β2 tanycytes contact not only de CSF but also the fenestrated capillaries (without barrier) of the median eminence, whereas β1 and α tanycytes processes contact blood vessels with barrier. In this regard, it has been demonstrated that β2 tanycytes are able to uptake hormones such a s ghrelin and leptin from the capillaries of the ME and then transfer them to β1 and α tanycytes, which release the hormones in close proximity to their target, the AN neurons42–44. Based on this evidence, it is feasible to propose that β2 tanycytes concentrate glucose in the CSF of the infundibular recess in order to be transferred to β1 and α tanycytes, being these populations the responsible of communicating glucose concentration to NA neurons. Of note, this glucosensing mechanism requires a rapid increase in CSF glucose levels, making it possible for the GK-positive glucosensing cells to generate acute responses.