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

我们小组从胃中发现了人类和老鼠的胃促生长素。胃促生长素。是一种新的激素，可以刺激生长激素（GH）的释放和食欲。从n端开始的第三个氨基酸丝氨酸被脂质正辛酸修饰，这种修饰对胃饥饿素的活性是必不可少的。在这项拨款期间，我们进行了以下关于胃饥饿素的研究。1、胃饥饿素在人胃中的分子形态在人胃中胃饥饿素主要以正辛烷基修饰形式存在。此外，我们还发现了四种较小的胃饥饿素分子形式。因此，在人胃中，胃饥饿素以多种形式存在，具有不同的氨基酸长度和酰基修饰。我们研究了胃对生长素产生的贡献。我们测量了全胃切除术前后的血浆胃饥饿素浓度。血浆ghrelin浓度下降约为术前的一半，并逐渐升高至接近正常水平。这一结果表明肠道和胰腺的胃饥饿素弥补了胃饥饿素的损失。3、非哺乳动物胃饥饿素的纯化和结构我们测定了两栖动物、鸟类和鱼类的胃饥饿素结构，发现胃饥饿素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、鸟类和鱼类的胃饥饿素中也发现了酰基修饰，就像哺乳动物的胃饥饿素一样。因此，胃饥饿素是一种保守的肽激素，对脊椎动物的生存至关重要。4、ghrelin - null小鼠的创建我们尝试创建ghrelin - null小鼠，并成功创建了ghrelin - null小鼠。我们现在正在研究它们的表型。

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.