Study for islet amyloid polypeptide and its gene, resolving etiology of Type 2 diabetes mellitus and developing diagnostic method for this disease.

在2型糖尿病中，病因仍有待阐明，但淀粉样蛋白沉积在胰岛内，并且胰岛淀粉样蛋白被认为与该疾病的发作或进展有关。1987年，胰岛淀粉样多肽（IAPP）作为胰岛淀粉样蛋白的主要成分被发现。因此，我们希望通过对该肽及其基因的研究，进一步阐明2型糖尿病的病因，并建立诊断2型糖尿病的方法。在第一年，我们计划分析IAPP基因，并建立该肽的免疫组织化学方法和放射免疫分析方法。用此寡肽免疫家兔，制备了抗IAPP的特异性抗体。这些方法是通过使用抗体和特异性的IAPP，因此，有用的岛叶淀粉样蛋白和IAPP的研究。由于在本研究的准备过程中发现了IAPP基因的序列，因此我们停止了对该基因的研究，第二年，我们计划对2型糖尿病患者的IAPP基因进行分析，并探讨其与糖尿病的关系。用直接测序法对IAPP基因进行了分析。用免疫组化法检测37例糖尿病患者胰岛淀粉样蛋白阳性率为75.6%。IAPP存在于胰腺B细胞中，并响应于葡萄糖与胰岛素共分泌。肥胖和糖尿病实验动物胰腺内IAPP含量和分泌增加，提示糖尿病患者胰腺内IAPP合成和分泌异常。建立了测定血中IAPP的方法，并测定了糖耐量减低和糖尿病患者的血浆IAPP水平。

In type 2 diabetes mellitus, etiology remains to be elucidated, but amyloid is deposited within pancreatic islets and insular amyloid has been thought to be related to onset or progression of this disease. In 1987, islet amyloid polypeptide (IAPP), a main component of insular amyloid, was identified. We proposed to study this peptide and its gene, resolving the etiology of type 2 diabetes mellitus and developing the diagnostic method for this disease. In the first year, we planned to analyze IAPP gene and to develop an immunohistochemical method and a radioimmunoassay method for this peptide. Specific antibodies for IAPP was produced by immunization of oligopeptide to rabbits. These methods were developed by using the antibodies and specific for IAPP, thus, useful for studies of insular amyloid and IAPP. Because sequence of IAPP gene had been reported during preparation of this study, we stopped to investegate it. In the second year, we proposed to analyze IAPP gene in type 2 diabetic patients and to investigate relationship between this disease and IAPP. IAPP gene has been analyzed by means of a direct sequencing method. Using immunohistochemical method, insular amyloid was observed to be in 75.6% of 37 diabetic patients. IAPP is present in pancreatic B-cells and cosecreted with insulin in response to glucose. IAPP content in pancreas and secretion were increased in obese and diabetic experimental animals, suggesting that synthesis and secretion are aberrant in diabetic patients. Method for measurement of IAPP in blood was developed, and plasma IAPP levels have been measured in subjects with impaired glucose tolerance and diabetes mellitus.