Non-acylated ghrelin counteracts the metabolic but not the neuroendocrine response to acylated ghrelin in humans
Non-acylated ghrelin counteracts the metabolic but not the neuroendocrine response to acylated ghrelin in humans
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DOI：
10.1210/jc.2003-031964
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发表时间：
2004-06-01
影响因子：
5.8
通讯作者：
Ghigo, E
中科院分区：
文献类型：
--
作者：
Broglio, F;Gottero, C;Ghigo, E
Ghrelin具有强烈的GH释放活性，但也具有其他内分泌活性，包括刺激PRL和ACTH分泌，调节胰岛素分泌和葡萄糖代谢。据推测，GH促分泌素（GHS）受体（GHS-R）1a介导生长素释放肽的作用，前提是其在丝氨酸3上的酰化;事实上，酰化的生长素释放肽只能发挥内分泌活性。酰化生长素释放肽（AG）在血清中的浓度比未酰化生长素释放肽（UAG）低2.5倍，然而，UAG不是生物学上无活性的;它与AG共享一些非内分泌作用，如心血管作用、细胞增殖的调节以及甚至对脂肪形成的一些影响。因此，这些行动可能是由GHS-R亚型能够独立于其酰化结合饥饿素介导的。为了进一步阐明UAG是否真的没有任何内分泌作用，我们在6名正常年轻志愿者（年龄[平均值+/- SE]：25.4 +/- 1.2岁; BMI：22.3 +/- 1.0 kg/m2）中研究了AG和UAG联合给药（1.0 mug/kg iv）的相互作用。如预期的，AG诱导循环GH、PRL、ACTH和皮质醇水平显著升高（p < 0.01）。AG给药后胰岛素水平也下降（-285.4+/-64.8 mU*min/l; p
Ghrelin possesses strong GH-releasing activity but also other endocrine activities including stimulation of PRL and ACTH secretion, modulation of insulin secretion and glucose metabolism. It is assumed that the GH Secretagogue (GHS) receptor (GHS-R) 1a mediates ghrelin actions provided its acylation in Serine 3; in fact, acylated ghrelin only is able to exert endocrine activities. Acylated ghrelin (AG) is present in serum at a 2.5 fold lower concentration than unacylated ghrelin (UAG).UAG, however, is not biologically inactive;it shares with AG some non-endocrine actions like cardiovascular effects,modulation of cell proliferation and even some influence on adipogensis. Thus, these actions are likely to be mediated by GHS-R subtypes able to bind ghrelin independently of its acylation. In order to further clarify whether UAG is really devoid of any endocrine action, we studied the interaction of the combined administration of AG and UAG (1.0 mug/kg iv) in 6 normal young volunteers (age [mean +/- SE]: 25.4 +/- 1.2 yr; BMI: 22.3 +/- 1.0 kg/m(2)). As expected, AG induced marked increase (p < 0.01) in circulating GH, PRL, ACTH and cortisol levels. AG administration was also followed by a decrease in insulin levels (-285.4+/-64.8 mU*min/l; p