Glucagon-like peptide 1 (GLP-1) suppresses ghrelin levels in humans via increased insulin secretion
Glucagon-like peptide 1 (GLP-1) suppresses ghrelin levels in humans via increased insulin secretion
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DOI：
10.1016/j.regpep.2007.03.002
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发表时间：
2007-10-04
影响因子：
--
通讯作者：
Meier, Juris J.
中科院分区：
文献类型：
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作者：
Hagemann, Dirk;Holst, Jens J.;Meier, Juris J.
Ghrelin是一种主要由胃分泌的促食欲肽。饥饿素血浆水平在进食前升高，进食后急剧下降，但控制饥饿素分泌的机制在很大程度上是未知的。由于膳食摄入也会促进肠促胰岛素激素胰高血糖素样肽1（GLP-1）的分泌，因此我们研究了外源性GLP-1给药是否会降低人体的ghrelin分泌。患者和方法：14名健康男性志愿者在390分钟内静脉输注GLP-1（1.2 pmol-kg（-1）min（-1））或安慰剂。30分钟后，提供固体试验餐。频繁抽取静脉血用于测定葡萄糖、胰岛素、C肽、GLP-1和ghrelin。结果如下：在输注外源性GLP-1和安慰剂期间，GLP-1血浆浓度分别达到139 +/- 15 pmol/l和12 +/- 2 pmol/l的稳态水平（p < 0.0001）。在安慰剂输注期间，饥饿素水平在餐后即刻显著降低（p < 0.001），之后再次升高。GLP-1给药防止了胃饥饿素水平的初始餐后下降，这可能是胃排空延迟的结果，并且显著降低了进食后150和360分钟的胃饥饿素水平（p < 0.05）。在GLP-1和安慰剂给药的实验中，生长素释放肽浓度的模式与胰岛素和C肽各自的血浆水平呈负相关。结论：GLP-1在超生理血浆水平降低餐后晚期ghrelin水平的升高。这些作用很可能是通过其促胰岛素作用间接介导的。GLP-1对ghrelin分泌的抑制作用可能与其抗肿瘤作用有关。(c)2007 Elsevier B.V保留所有权利。
Introduction: Ghrelin is an orexigenic peptide predominantly secreted by the stomach. Ghrelin plasma levels rise before meal ingestion and sharply decline afterwards, but the mechanisms controlling ghrelin secretion are largely unknown. Since meal ingestion also elicits the secretion of the ineretin hormone glucagon-like peptide 1 (GLP-1), we examined whether exogenous GLP-1 administration reduces ghrelin secretion in humans. Patients and methods: 14 healthy male volunteers were given intravenous infusions of GLP-1(1.2 pmol-kg(-1) min(-1)) or placebo over 390 min. After 30 min, a solid test meal was served. Venous blood was drawn frequently for the determination of glucose, insulin, C-peptide, GLP-1 and ghrelin. Results: During the infusion of exogenous GLP-1 and placebo, GLP-1 plasma concentrations reached steady-state levels of 139 +/- 15 pmol/1 and 12 +/- 2 pmol/l, respectively (p < 0.0001). During placebo infusion, ghrelin levels were significantly reduced in the immediate postprandial period (p < 0.001), and rose again afterwards. GLP-1 administration prevented the initial postprandial decline in ghrelin levels, possibly as a result of delayed gastric emptying, and significantly reduced ghrelin levels 150 and 360 min after meal ingestion (p < 0.05). The patterns of ghrelin concentrations in the experiments with GLP-1 and placebo administration were inversely related to the respective plasma levels of insulin and C-peptide. Conclusions: GLP-1 reduces the rise in ghrelin levels in the late postprandial period at supraphysiological plasma levels. Most likely, these effects are indirectly mediated through its insulinotropic action. The GLP-1-induced suppression of ghrelin secretion might be involved in its anorexic effects. (c) 2007 Elsevier B.V All rights reserved.