Inhibitory effect of exogenous orexin a on gastric emptying, plasma leptin, and the distribution of orexin and orexin receptors in the gut and pancreas in man
Inhibitory effect of exogenous orexin a on gastric emptying, plasma leptin, and the distribution of orexin and orexin receptors in the gut and pancreas in man
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DOI：
10.1210/jc.2004-1408
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发表时间：
2005-04-01
影响因子：
5.8
通讯作者：
Näslund, E
中科院分区：
文献类型：
--
作者：
Ehrström, M;Gustafsson, T;Näslund, E
食欲素A（OXA）是一种新型肽，似乎在调节食物摄入、唤醒和能量平衡中发挥作用。本研究的目的是研究静脉输注OXA对人（6名正常男性）胃排空、食欲、瘦素、生长素释放肽和葡萄糖代谢的影响以及OXA和食欲素受体（OXRs）1和2在人肠道中的定位。在摄取Tc-99 m标记的煎蛋卷和静脉输注OXA（10 pmol/ kg中心点min）后，通过放射性造影研究胃排空。定期获得食欲评级和血液样本。使用识别OXA、OX 1 R和OX 2 R的抗体检测人胃肠道组织中OXA和OXRs的免疫组织化学分布。OXA对滞后期或胃半排空时间无影响。然而，胃排空率显著减慢，而不影响食欲评分。胰岛素的血浆浓度增加OXA，而血浆瘦素下降和ghrelin不变。在胃和小肠的粘膜、神经节和环形肌肉层的神经元和静脉曲张神经纤维以及粘膜内分泌细胞中观察到OXA免疫反应性。胰岛中的OXA免疫反应性细胞含有胰岛素，其中一个子集表达OX 2 R。总之，外周OXA似乎轻微影响人类胃排空的调节，而不影响食欲评级。OXA降低血浆瘦素水平，表明瘦素和OXA之间可能存在相互作用，调节能量稳态。
Orexin A (OXA) is a novel peptide that appears to play a role in the regulation of food intake, arousal, and energy balance. The aim of this study was to study the effect of iv infusion of OXA on gastric emptying, appetite, leptin, ghrelin, and glucose metabolism in man ( six normal men) and the localization of OXA and orexin receptors (OXRs) 1 and 2 in the human gut. Gastric emptying was studied scintigraphically after ingestion of a Tc-99m-labeled omelet and iv infusion of OXA ( 10 pmol/ kg center dot min). Appetite ratings and blood samples were obtained at regular intervals. The immunohistochemical distribution of OXA and OXRs was examined using antibodies recognizing OXA, OX1R, and OX2R in human gastrointestinal tissue. OXA had no effect on lag phase or gastric half-emptying time. However, the gastric emptying rate was significantly slower without affecting appetite ratings. Plasma concentrations of insulin were increased by OXA, whereas plasma leptin decreased and ghrelin was unchanged. OXA immunoreactivity was observed in a subset of neurons and varicose nerve fibers in the mucosa, ganglia, and circular muscle layer and mucosal endocrine cells in the stomach and small intestine. OXA-immunoreactive cells in the islets of Langerhans contained insulin with a subset expressing OX2R. In conclusion, peripheral OXA seems to slightly affect the regulation of gastric emptying in humans without affecting appetite ratings. OXA decreased plasma levels of leptin, suggesting a possible interaction between leptin and OXA in the regulation of energy homeostasis.