Study on the relationship between expression of islet amyloid polypeptide and onset of type 2 diabetes mellitus.

在2型糖尿病中，淀粉样蛋白沉积在胰岛内，并且胰岛淀粉样蛋白被认为与这种疾病的发作或进展有关。1987年，胰岛淀粉样蛋白多肽（IAPP），这种淀粉样蛋白的主要成分，被确定。本研究拟探讨IAPP基因表达与该病发生、发展的关系。我们使用放射免疫分析系统测量了腹内侧损伤大鼠、肥胖Zucker大鼠和遗传性肥胖小鼠的胰岛中IAPP含量。肥胖和糖尿病动物的IAPP含量增加。我们观察到IAPP在一种新的胰腺β细胞系中的表达; MIN 6来源于转基因小鼠胰岛素瘤。该细胞系为研究IAPP的合成和分泌奠定了基础。我们用聚合酶链反应直接测序法检测了2型糖尿病患者IAPP基因5 '上游。在该区域观察到一个碱基的多态性，但该多态性与该疾病无关。我们成功地建立了表达人IAPP的转基因小鼠。证实人IAPP在小鼠的胰腺β细胞中特异性表达。转基因小鼠有望成为研究人IAPP基因表达与2型糖尿病发病或进展关系的有效工具。

In type 2 diabetes mellitus, 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 major component of this amyloid, was identified. We proposed to resolve the relationship between expression of IAPP gene and onset or progression of this disease. We measured IAPP content in the pancreatic islets of ventro-medial lesioned rats, obese Zucker rats and genetically obese mice, using a radioimmunoassay system. IAPP contents increased in these obese and diabetic animals. We observed expression of IAPP in a new pancreatic beta-cell line; MIN6 derived from transgenic mouse insulinoma. This cell line would be useful for study on IAPP synthesis and secretion. We examined 5'-upstream of IAPP gene of type 2 diabetic subjects by means of direct sequence using polymerase chain reaction. Polymorphism of one base in this region was observed, but this polymorphism was not related to this disease. We succeeded in the production of transgenic mouse expressing human IAPP. Human IAPP was confirmed to be specifically expressed in the pancreatic beta-cells of the mouse. The transgenic mouce should be a useful tool for resolving the relationship between expression of human IAPP gene and onset or progression of type 2 diabetes mellitus.