Repeated glucoprivation delayed hyperphagic responses while activating neuropeptide Y neurons in rats

It is well known that glucoprivation induces the release of counterregulatory hormones such as glucagon, and that the response is attenuated when the stimuli are repeated. Glucoprivation also activates orexigenic neurons and induces hyperphagic responses, although it remains unclear whether these responses are attenuated in repeated glucoprivation. In this study, we examined time course changes in feeding as well as activities of orexigenic neuropeptide Y (NPY) neurons in repeated glucoprivation in rats. Either 2-deoxy-d-glucose (2DG), which blocks glucose utilization, or isotonic saline (control) was injected subcutaneously to rats for 14 days, and food consumption for 1 and 2 h after injection was monitored throughout the experiment. While 2DG injection induced robust feeding responses during the first 1 h after injection, the response was gradually attenuated and the food consumption was significantly less on days 12-14 compared to that on day 1. On the other hand, food consumption during 2 h after 2DG injection was not changed significantly for 14 days. The transcriptional activities of NPY neurons in the arcuate nucleus and C1/A1 region of the hindbrain, measured by intronic in situ hybridization, were significantly enhanced after repeated 2DG injection for 14 days, while the feeding responses to intracerebroventricular injection of NPY were significantly less in the 2DG-repeated group compared to the saline-repeated group. It is thus demonstrated that repeated glucoprivation delayed hyperphagic responses while activating NPY neurons in rats. Our data also suggest that decreased feeding responses to NPY might be at least partially responsible for the delayed response.