Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans

Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans
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DOI:
10.1210/jc.86.10.4753
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发表时间:
2001-10-01
影响因子:
5.8
通讯作者:
Nakao, K
Nakao, K
中科院分区:
医学2区
文献类型:
--
作者:
Ariyasu, H;Takaya, K;Nakao, K

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Ghrelin是GH促分泌剂受体的内源性配体,是从大鼠胃中分离出来的,参与了一个新的GH释放调节系统。虽然以前对啮齿动物的研究表明,ghrelin也参与了能量平衡,而且ghrelin的分泌受到摄食的影响,但对人类血浆ghrelin的了解很少。为了解决这个问题,我们研究了人类血浆Ghrelin样免疫反应水平,并阐明了循环中Ghrelin的来源以及喂养状态对血浆Ghrelin样免疫反应水平的影响。用放射免疫法测定正常人血浆Ghrelin样免疫反应浓度为166.0+/-10.1fmol/ml。Northern印迹分析表明,胃和血浆中Ghrelin基因表达最丰富。全胃切除患者的类免疫反应水平降至正常对照组的35%。禁食12h后血浆Ghrelin样免疫反应水平升高31%,习惯性喂养后即刻降低22%。神经性厌食症患者血浆Ghrelin样免疫反应水平显著高于正常对照组(401.2±58.4fmol/ml对192.8+/-19.4fmol/ml),且与体重指数呈负相关。我们的结论是,胃是循环Ghrelin的主要来源,血浆Ghrelin样免疫反应水平反映了人类的急性和慢性喂养状态。
Ghrelin, an endogenous ligand for the GH secretagogue receptor, was isolated from rat stomach and is involved in a novel system for regulating GH release. Although previous studies in rodents suggest that ghrelin is also involved in energy homeostasis and that ghrelin secretion is influenced by feeding, little is known about plasma ghrelin in humans. To address this issue, we studied plasma ghrelin-like immunoreactivity levels and elucidated the source of circulating ghrelin and the effects of feeding state on plasma ghrelin-like immunoreactivity levels in humans. The plasma ghrelin-like immunoreactivity concentration in normal humans measured by a specific RIA was 166.0 +/- 10.1 fmol/ml. Northern blot analysis of various human tissues identified ghrelin mRNA found most abundantly in the stomach and plasma ghrelin. like immunoreactivity levels in totally gastrectomized patients were reduced to 35% of those in normal controls. Plasma ghrelin-like immunoreactivity levels were increased by 31% after 12-h fasting and reduced by 22% immediately after habitual feeding. In patients with anorexia nervosa, plasma ghrelin-like immunoreactivity levels were markedly elevated compared with those in normal controls (401.2 +/- 58.4 vs. 192.8 +/- 19.4 fmol/ml) and were negatively correlated with body mass indexes. We conclude that the stomach is a major source of circulating ghrelin and that plasma ghrelin-like immunoreactivity levels reflect acute and chronic feeding states in humans.