PACAP deficient mice display reduced carbohydrate intake and PACAP activates NPY-containing neurons in the rat hypothalamic arcuate nucleus
PACAP deficient mice display reduced carbohydrate intake and PACAP activates NPY-containing neurons in the rat hypothalamic arcuate nucleus
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DOI：
10.1016/j.neulet.2004.08.034
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发表时间：
2004-11-11
影响因子：
2.5
通讯作者：
Yada, T
中科院分区：
文献类型：
--
作者：
Nakata, M;Kohno, D;Yada, T
腺苷酸环化酶激活多肽（PACAP）可增强胰岛的胰岛素释放和脂肪细胞的胰岛素作用。因此，这种肽被认为是葡萄糖稳态的调节剂。PACAP及其受体不仅定位于外周组织，而且定位于中枢神经系统。本研究探讨了PACAP是否调节摄食行为和摄食中枢下丘脑弓状核（ARC）神经元的活动。在PACAP敲除小鼠中测量食物摄入。用Fura-2显微荧光法测定分离自大鼠ARC的单个神经元胞内Ca ~（2+）浓度（[Ca ~（2+）]（i）），然后用抗NPY抗血清进行免疫细胞化学染色。PACAP基因敲除的小鼠表现出高碳水化合物食物摄入量的减少，但高脂肪食物的摄入量没有减少。PACAP增加ARC中与摄食，特别是碳水化合物摄入有关的NPY神经元中的[Ca 2 +]（i）。PACAP受体激动剂PAC 1-R和VPAC 2-R也增加[Ca 2 +]（i）。本研究通过证明PACAP直接与ARC NPY神经元反应以增加[Ca 2 +]（i），并且在PACAP缺乏时摄入富含碳水化合物的食物减少，表明PACAP在碳水化合物摄入中的促进作用。(C)2004爱思唯尔爱尔兰有限公司保留所有权利。
Pituitary adenylate cyclase-activating polypeptide (PACAP) potentiates both insulin release from islets and insulin action in adipocytes. Therefore, this peptide is considered a regulator of glucose homeostasis. PACAP and its receptors are localized not only in the peripheral tissues but in the central nervous system. The present study examined whether PACAP regulates the feeding behavior and the activity of neurons in the hypothalamic arcuate nucleus (ARC), a feeding center. Food intake was measured in the PACAP knock-out mice. Cytosolic Ca2+ concentration ([Ca2+](i)) in single neurons isolated from the ARC of rats was measured by fura-2 microfluorometry, followed by immunocytochemical staining with anti-NPY antiserum. PACAP knock-out mice showed a decrease in the intake of high carbohydrate, but not high fat, food. PACAP increased [Ca2+](i) in NPY neurons of the ARC that are implicated in the feeding, particularly the carbohydrate ingestion. Agonists of PACAP receptors, PAC1-R and VPAC2-R, also increased [Ca2+](i). The present study, by demonstrating that PACAP directly reacts with the ARC NPY neurons to increase [Ca2+](i) and that ingestion of the carbohydrate-rich food is reduced in PACAP-deficiency, suggests a facilitative role for PACAP in the carbohydrate intake. (C) 2004 Elsevier Ireland Ltd. All rights reserved.