Energy expenditure by intravenous administration of glucagon-like peptide-1 mediated by the lower brainstem and sympathoadrenal system

Energy expenditure by intravenous administration of glucagon-like peptide-1 mediated by the lower brainstem and sympathoadrenal system
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DOI:
10.1016/j.peptides.2005.02.016
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发表时间:
2005-09-01
期刊:
影响因子:
3
通讯作者:
Inoue, S
Inoue, S
中科院分区:
医学3区
文献类型:
--
作者:
Osaka, T;Endo, M;Inoue, S

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胰升糖素样肽-1(GLP-1)是在营养摄入后从肠道释放出来的。静脉注射GLP-1(50pmol-20nmol)可引起乌拉坦麻醉大鼠全身氧耗率(VO2)、能量消耗指数和心率的剂量依赖性增加。体心(结肠)温度上升到0.3摄氏度,尾部皮肤温度没有变化。侧脑室(Icv)注射GLP-1引起的VO2增加比静脉注射慢且小。注射胰升糖素样肽-2(iv或icv)对VO2、体温和心率均无影响。去大脑对静脉注射GLP-1引起的发热反应没有影响,表明前脑对这些反应不是必需的。然而,颈椎横断极大地减弱了反应,表明下部脑干是关键受累部位。肾上腺切除或使用自主神经节阻滞剂六甲溴铵或β肾上腺素能阻滞剂心得安也可显著减弱致精原反应。然而,隔膜下迷走神经切断术或腹膜-肠系膜上神经节切除术没有效果。用链脲佐菌素预处理造成胰岛素缺乏的大鼠也表现出对GLP-1的正常生热反应。这些结果表明,GLP-1参与了由下部脑干和交感肾上腺系统调节的餐后能量消耗。(C)2005 Elsevier Inc.保留所有权利。
Glucagon-like peptide-1 (GLP-1) is released from the gut in response to nutrient ingestion. Intravenous (iv) administration of GLP-1 (50 pmol-20 nmol) elicited dose-dependent increases in the rate of whole-body O-2 consumption (VO2), an index of energy expenditure, and heart rate of urethane-anesthetized rats. The body core (colonic) temperature increased up to 0.3 degrees C without accompanying alteration of tail skin temperature. Intracerebroventricular (icv) administration of GLP-1 induced a slower and smaller increase in VO2, than the intravenous administration. The injection of glucagon-like peptide-2 (iv or icv) had no effect on VO2, body temperatures, or heart rate. Decerebration had no effect on the thermogenic responses induced by the iv administration of GLP-1, suggesting that the forebrain is not essential for these responses. However, cervical spinal transection greatly attenuated the responses, suggesting the critical involvement of the lower brainstem. Adrenalectomy or pretreatment with an autonomic ganglion blocker, hexamethonium, or a beta-adrenergic blocker, propranolol, also significantly attenuated the themiogenic response. However, subdiaphragmatic vagotomy or celiac-superior mesenteric ganglionectomy had no effect. Rats made insulin-deficient by pretreatment with streptozotocin also exhibited the normal thermogenic response to GLP-1. These results suggest the involvement of the GLP-1 in postprandial energy expenditure, mediated by the lower brainstem and sympathoadrenal system. (c) 2005 Elsevier Inc. All rights reserved.