Sindelar Dana K, Ste Marie Linda, Miura Grant I, Palmiter Richard D, McMinn Julie E, Morton Gregory J, Schwartz Michael W
Department of Medicine, Harborview Medical Centr, Howard Hughes Medical Institute, University of Washington, Seattle 98195, USA.
Endocrinology. 2004 Jul;145(7):3363-8. doi: 10.1210/en.2003-1727. Epub 2004 Apr 2.
To investigate the role played by the orexigenic peptide, neuropeptide Y (NPY), in adaptive responses to insulin-induced hypoglycemia, we measured hypothalamic, feeding, and hormonal responses to this stimulus in both wild-type (Npy+/+) and NPY-deficient (Npy-/-) mice. After administration of insulin at a dose (60 mU ip) sufficient to cause moderate hypoglycemia (plasma glucose levels, 40 +/- 3 and 37 +/- 2 mg/dl for Npy+/+ and Npy-/- mice, respectively; P = not significant), 4-h food intake was increased 2.5-fold in Npy+/+ mice relative to saline-injected controls. By comparison, the increase of intake in Npy-/- mice was far smaller (45%) and did not achieve statistical significance (P = 0.08). Hyperphagic feeding in response to insulin-induced hypoglycemia was therefore markedly attenuated in mice lacking NPY, and a similar feeding deficit was detected in these animals after neuroglucopenia induced by 2-deoxyglucose (500 mg/kg ip). A role for NPY in glucoprivic feeding is further supported by our finding that Npy mRNA content (measured by real-time PCR) increased 2.4-fold in the hypothalamus of Npy+/+ mice by 7 h after insulin injection. Unlike the feeding deficits observed in mice lacking NPY, the effect of hypoglycemia to increase plasma glucagon and corticosterone levels was fully intact in these animals, as were both the nadir glucose value and time to recovery of euglycemia after insulin injection (P = not significant). We conclude that NPY signaling is required for hyperphagic feeding, but not neuroendocrine responses to moderate hypoglycemia.
为了研究促食欲肽神经肽Y（NPY）在对胰岛素诱导的低血糖的适应性反应中所起的作用，我们在野生型（Npy+/+）和NPY缺陷型（Npy-/-）小鼠中测量了对该刺激的下丘脑、进食及激素反应。以足以引起中度低血糖的剂量（腹腔注射60 mU）给予胰岛素后（Npy+/+和Npy-/-小鼠的血浆葡萄糖水平分别为40±3和37±2 mg/dl；P值无统计学意义），与注射生理盐水的对照组相比，Npy+/+小鼠4小时的食物摄入量增加了2.5倍。相比之下，Npy-/-小鼠的摄入量增加要小得多（45%），且未达到统计学意义（P = 0.08）。因此，在缺乏NPY的小鼠中，对胰岛素诱导的低血糖的摄食亢进明显减弱，并且在这些动物经2-脱氧葡萄糖（腹腔注射500 mg/kg）诱导出现神经低血糖症后也检测到类似的进食缺陷。我们发现胰岛素注射7小时后，Npy+/+小鼠下丘脑的Npy mRNA含量（通过实时PCR测量）增加了2.4倍，这进一步支持了NPY在糖缺乏性进食中的作用。与在缺乏NPY的小鼠中观察到的进食缺陷不同，低血糖增加血浆胰高血糖素和皮质酮水平的作用在这些动物中完全正常，胰岛素注射后的最低血糖值及血糖恢复正常的时间也是如此（P值无统计学意义）。我们得出结论，NPY信号传导是摄食亢进所必需的，但不是对中度低血糖的神经内分泌反应所必需的。
