A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans
A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans
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DOI：
10.2337/diabetes.50.8.1714
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发表时间：
2001-08-01
期刊：
影响因子：
7.7
通讯作者：
Weigle, DS
中科院分区：
文献类型：
--
作者：
Cummings, DE;Purnell, JQ;Weigle, DS
最近发现的促食欲肽ghrelin主要由胃产生，并在大鼠长时间禁食期间以增加的水平在血液中循环。当以超生理剂量给予啮齿动物时，ghrelin激活下丘脑神经肽Y/agrelin基因相关蛋白神经元并增加食物摄入和体重。这些结果表明，胃饥饿素可能参与膳食启动。作为研究这一假设的第一步，我们试图确定在人类食用单独的膳食之前循环ghrelin水平是否升高。在10名健康受试者的24小时内，通过放射免疫法测定了38次血浆样本中的Ghrelin、胰岛素和瘦素，这些受试者按固定时间表提供膳食。血浆ghrelin水平在每餐前增加近两倍，并在进食后1小时内降至谷水平，与胰岛素的模式相反。餐间生长激素释放肽水平显示出与瘦素完全同步的昼夜节律，这两种激素在一天中上升到0100的顶点，然后在一夜之间下降到0900的最低点。在早餐前后的波谷采样的Ghrelin水平与24小时积分曲线下面积值（r = 0.873和0.954，分别）强烈相关，这表明这些方便的，单一的测量可能作为替代24小时的配置文件，以估计整体ghrelin水平。循环ghrelin也与年龄呈正相关（r = 0.701）。血浆胃饥饿素水平在餐前明显上升和餐后下降支持了胃饥饿素在人类膳食启动中发挥生理作用的假设。
The recently discovered orexigenic peptide ghrelin is produced primarily by the stomach and circulates in blood at levels that increase during prolonged fasting in rats. When administered to rodents at supraphysiological doses, ghrelin activates hypothalamic neuropeptide Y/agouti gene-related protein neurons and increases food intake and body weight. These findings suggest that ghrelin may participate in meal initiation. As a first step to investigate this hypothesis, we sought to determine whether circulating ghrelin levels are elevated before the consumption of individual meals in humans. Ghrelin, insulin, and leptin were measured by radio-immunoassay in plasma samples drawn 38 times throughout, a 24-h period in 10 healthy subjects provided meals on a fixed schedule. Plasma ghrelin levels increased nearly twofold immediately before each meal and fell to trough levels within 1 h after eating, a pattern reciprocal to that of insulin. Intermeal ghrelin levels displayed a diurnal rhythm that was exactly in phase with that of leptin, with both hormones rising throughout the day to a zenith at 0100, then falling overnight to a nadir at 0900. Ghrelin levels sampled during the troughs before and after breakfast correlated strongly with 24-h integrated area under the curve values (r = 0.873 and 0.954, respectively), suggesting that these convenient, single measurements might serve as surrogates for 24-h profiles to estimate overall ghrelin levels. Circulating ghrelin also correlated positively with age (r = 0.701). The clear preprandial rise and postprandial fall in plasma ghrelin levels support the hypothesis that ghrelin plays a physiological role in meal initiation in humans.