Application of ghrelin for diagnosis and treatment of endocrine and metabolic diseases.

我们小组从胃中发现了人和大鼠的胃促生长素。生长激素释放素。是一种新的激素，能刺激生长激素(GH)的释放和食欲。N端的第三个氨基酸丝氨酸被脂类正辛酸修饰，这种修饰对Ghrelin的活性是必不可少的。在本次资助期间，我们对Ghrelin进行了以下研究：1.人胃中Ghrelin的分子形式主要以正辛酰修饰形式存在。此外，我们还发现了Ghrelin的四种次要分子形式。因此，在人的胃中，胃促生长素以多种形式存在，具有不同的氨基酸长度和酰基修饰。2.我们研究了胃对胃促生长素产生的贡献。测定全胃切除手术前后血浆Ghrelin浓度。血浆Ghrelin浓度降至术前的一半左右，并逐渐回升至接近正常水平。这一结果表明肠道和胰腺Ghrelin弥补了胃Ghrelin的损失。3、非哺乳动物Ghrelin的纯化和结构我们测定了两栖动物、鸟类和鱼类Ghrelin的结构，发现Ghrelin不仅存在于哺乳动物中，而且存在于所有脊椎动物中。此外，在两栖动物、鸟类和鱼类中发现了Ghrelin的酰基化修饰，就像哺乳动物的Ghrelin一样。因此，Ghrelin是一种保守的多肽荷尔蒙，对脊椎动物的生存是必不可少的。4，Ghrelin缺失小鼠的创建我们试图创造Ghrelin缺失小鼠，并成功地创造了Ghrelin缺失小鼠。我们现在正在调查他们的表型。

Our group discovered human and rat ghrelins from stomach. Ghrelin. is a novel hormone, which stimulates growth hormone (GH) release and appetite. The third amino-acid serine from the N-terminal end is modified by a lipid n-octanoic acid and this modification is essential for ghrelin activity. In the period of this grant, we performed following research on ghrelin.1, Molecular forms of ghrelin in human stomach In human stomach ghrelin existed mainly as the n-octanoyl modified form. In addition, we found four minor molecular forms of ghrelin. Thus, in human stomach ghrelin existed as multiple forms with various amino-acid lengths and acyl-modifications.2, We examined the contribution of stomach for the production of ghrelin. We measured plasma ghrelin concentrations before and after total gastrectomy operation. Plasma ghrelin concentration was decreased approximately to half that of before the operation, and gradually increased to near normal level. This result indicates that intestinal and pancreatic ghrelins compensate the loss of gastric ghrelin.3, Purifications and structures of non-mammalian ghrelins We determined the structures of amphibian, bird, and fish ghrelins, and found that ghrelin existed not only in mammals but also in all vertebrate species. Moreover, acyl-modification of ghrelin is found in amphibian, bird, and fish ghrelins, as like mammalian ghrelins. Thus, ghrelin is a well-conserved peptide hormone that is essential for survival of vertebrates.4, Creation of ghrelin null-mice We tried to create ghrelin null-mice and succeeded in creating ghrelin null-mice. We are now investigating their phenotypes.