Intrameal Hepatic Portal and Intraperitoneal Infusions of Glucagon-Like Peptide-1 Reduce Spontaneous Meal Size in the Rat via Different Mechanisms
Intrameal Hepatic Portal and Intraperitoneal Infusions of Glucagon-Like Peptide-1 Reduce Spontaneous Meal Size in the Rat via Different Mechanisms
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DOI：
10.1210/en.2008-1221
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发表时间：
2009-03-01
期刊：
影响因子：
4.8
通讯作者：
Langhans, Wolfgang
中科院分区：
文献类型：
--
作者：
Ruettimann, Elisabeth B.;Arnold, Myrtha;Langhans, Wolfgang
外周应用胰升糖素样肽-1(GLP-1)可减少动物和人类的摄食量，但这种作用的部位、机制及其生理意义尚不清楚。为了研究这些问题，我们准备了慢性导管的大鼠，并在第一次自发的暗相进餐中输入GLP-1(0.2ml/min；2.5或5.0min)。在进餐后2-3分钟远程触发输液。肝门静脉(HPV)输注1.0或3.0(但不是0.33)nmol/kg GLP-1可减少持续进餐的大小，而不影响随后的进餐间隔、后续进餐的大小或累积食物摄入量。在双管大鼠中，HPV和腔静脉注入1.0nmol/kg GLP-1类似地减少了食物的体积。在隔膜下迷走神经去传入的大鼠和假手术大鼠中，注射1.0nmol/kg GLP-1的HPV GLP-1也同样减少了食物的大小。最后，HPV和IP注射10nmol/kg GLP-1可类似地减少假手术大鼠的进食大小，但仅HPV GLP-1可减少隔膜下迷走神经传入大鼠的进食大小。这些数据表明，外周输注GLP-1可以显著和特异地减少大鼠持续进餐的数量，ip而不是iv的饱腹感需要迷走神经传入信号。这些发现表明，静脉注射GLP-1不会通过肝脏门脉或肝脏GLP-1受体抑制进食，但可能直接作用于大脑。(内分泌学150：1174-1181,2009)
Peripheral administration of glucagon-like peptide (GLP)-1 reduces food intake in animals and humans, but the sites and mechanism of this effect and its physiological significance are not yet clear. To investigate these issues, we prepared rats with chronic catheters and infused GLP-1 (0.2 ml/min; 2.5 or 5.0 min) during the first spontaneous dark-phase meals. Infusions were remotely triggered 2-3 min after meal onset. Hepatic portal vein (HPV) infusion of 1.0 or 3.0 (but not 0.33) nmol/kg GLP-1 reduced the size of the ongoing meal compared with vehicle without affecting the subsequent intermeal interval, the size of subsequent meals, or cumulative food intake. In double-cannulated rats, HPV and vena cava infusions of 1.0 nmol/kg GLP-1 reduced meal size similarly. HPV GLP-1 infusions of 1.0 nmol/kg GLP-1 also reduced meal size similarly in rats with subdiaphragmatic vagal deafferentations and in sham-operated rats. Finally, HPV and ip infusions of 10 nmol/kg GLP-1 reduced meal size similarly in sham-operated rats, but only HPV GLP-1 reduced meal size in subdiaphragmatic vagal deafferentation rats. These data indicate that peripherally infused GLP-1 acutely and specifically reduces the size of ongoing meals in rats and that the satiating effect of ip, but not iv, GLP-1 requires vagal afferent signaling. The findings suggest that iv GLP-1 infusions do not inhibit eating via hepatic portal or hepatic GLP-1 receptors but may act directly on the brain. (Endocrinology 150: 1174-1181, 2009)