Cellular Physiology and molecular biology of amylin in NIDDM

胰淀素，又称胰岛淀粉样蛋白多肽，是1987年从胰岛淀粉样蛋白中分离得到的一种含有37个氨基酸的肽。该肽被认为通过在外周组织中抵抗胰岛素的作用和通过淀粉样蛋白沉积破坏胰岛结构而参与NIDDM的病因学。我们研究了胰淀素的特性，它在糖耐量异常中的合成和分泌，以及NIDDM中胰岛淀粉样蛋白的形成。我们开发了三种针对胰淀素的ria：人和大鼠胰淀素共同n端区域，人和大鼠胰淀素c端区域。我们还在许多哺乳动物的胰腺、胃肠道和血浆中发现了内源性的胰淀素分子形式。胰淀素信使RNA的大小为900个碱基，主要在胰腺中表达。大鼠胎儿胰腺中检测到胰淀素，其含量在发育过程中逐渐增加。出生后3天，胃窦出现胰淀素。在人类胰腺中，胰淀素在妊娠15周时被检测到。胰腺胰胰素含量为221.6<正负> /g湿重78.2 pmol/g，大鼠为328.5<正负>25.0 pmol/g湿重，约为胰岛素含量的1-2%。正常人的基础血浆免疫反应性amylin水平为2.4-5.8 fmol/ml，在肥胖或糖耐量受损的受试者中升高，在糖尿病患者中降低。胰岛淀粉样蛋白沉积不是NIDDM的主要病因，然而，淀粉样蛋白沉积可能加剧胰岛功能障碍并促进NIDDM的进展。

Amylin, also designated islet amyloid polypeptide, is a 37-amino acid peptide that was isolated from islet amyloid in 1987. The peptide is thought to be involved in the etiology of NIDDM by opposing insulin action in peripheral tissues and by destroying islet construction through amyloid deposition. We studied the properties of amylin, its synthesis and secretion in abnormal glucose tolerance, and amyloidogenesis of the islet in NIDDM.We developed three RIAs for amylin : human and rat common N-terminal region of amylin, and both human and rat C-terminal amylin. We also identified endogenous molecular forms of amylin in pancreata, gastrointestinal tracts and plasma of many mammals. Amylin messenger RNA whose size is 900 bases is predminantly expressed in the pancreas. Amylin is detected in rat fetal pancreas, and its content gradually increases during development. Amylin in the antrum appears 3 days after birth. In the human pancreas, amylin is detected at 15 weeks of gestation. Pancreatic amylin content was 221.6<plus-minus>78.2 pmol/g wet weight in man and 328.5<plus-minus>25.0 pmol/g wet weight in rat, being approximately 1-2% of insulin content. Basal plasma immunoreactive amylin level in normal individuals was 2.4-5.8 fmol/ml, being increased in subjects with ovesity or impaired glucose tolerance, and decreased in diabetic patients. Amylin was co-secreted with insulin in physiological conditiIslet amyloid deposition is not responsible for the primary etiology of NIDDM,however, the amyloid deposits could intensify islet dysfunction and contribute to the progression of NIDDM.