Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Peptides. 2011 Apr;32(4):763-9. doi: 10.1016/j.peptides.2010.12.009. Epub 2010 Dec 22.
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 2h after injection was monitored throughout the experiment. While 2DG injection induced robust feeding responses during the first 1h 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 2h 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.
众所周知，糖剥夺会引起胰高血糖素等激素的释放，而当刺激重复时，这种反应会减弱。糖剥夺还会激活摄食神经元并引起多食反应，尽管尚不清楚这些反应在重复糖剥夺时是否会减弱。在这项研究中，我们检查了重复糖剥夺对大鼠摄食和食欲神经肽 Y (NPY) 神经元活性的时间进程变化。2-脱氧-D-葡萄糖（2DG），它阻止葡萄糖利用，或等渗盐水（对照）被皮下注射到大鼠中 14 天，并在整个实验过程中监测注射后 1 和 2 小时的食物消耗。虽然 2DG 注射在注射后 1 小时内引起了强烈的摄食反应，但随着时间的推移，反应逐渐减弱，与第 1 天相比，第 12-14 天的食物消耗明显减少。另一方面，2DG 注射后 2 小时内的食物消耗在 14 天内没有明显变化。通过内含子原位杂交测量，弓状核和后脑 C1/A1 区域的 NPY 神经元的转录活性在重复 2DG 注射 14 天后显著增强，而向侧脑室注射 NPY 引起的摄食反应在 2DG 重复组明显低于盐水重复组。因此，在大鼠中，重复糖剥夺延迟了多食反应，同时激活了 NPY 神经元。我们的数据还表明，对 NPY 的摄食反应减少至少部分是导致反应延迟的原因。
