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

ghrelin在内分泌代谢疾病诊断和治疗中的应用。

基本信息

批准号：
14370331
负责人：
KOJIMA Masayasu
金额：
$ 9.66万
依托单位：
Kurume University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

项目摘要

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.

我们的小组从胃中发现了人类和大鼠的胃饥饿素。胃饥饿素。是一种新型激素，可刺激生长激素 (GH) 释放和食欲。 N 末端的第三个氨基酸丝氨酸被脂质正辛酸修饰，这种修饰对于生长素释放肽活性至关重要。在本资助期间，我们对ghrelin进行了以下研究。 1、人胃中ghrelin的分子形式人胃中ghrelin主要以正辛酰修饰形式存在。此外，我们还发现了四种小分子形式的生长素释放肽。因此，在人胃中ghrelin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ghrelin产生的贡献。我们测量了全胃切除术前后的血浆生长素释放肽浓度。血浆ghrelin浓度大约下降至术前的一半，并逐渐升高至接近正常水平。这一结果表明肠道和胰腺ghrelin补偿了胃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，而且存在于哺乳动物中。所有脊椎动物。此外，与哺乳动物的生长素释放肽一样，生长素释放肽的酰基修饰存在于两栖动物、鸟类和鱼类的生长素释放肽中。因此，ghrelin是一种非常保守的肽类激素，对于脊椎动物的生存至关重要。4、ghrelin无效小鼠的创建我们尝试创建ghrelin无效小鼠并成功创建了ghrelin无效小鼠。我们现在正在研究它们的表型。