PANCREATIC HORMONES

描述（改编自申请人的摘要）： 这项研究计划是为了获得对分子和细胞的新见解， 胰岛素产生和作用的生物学机制， 胰岛的相关肽激素，包括其 遗传基础，进化起源，以及这些过程中的疾病， 可能导致糖尿病和/或其它疾病的病理生理学。 新的项目和以前工作的扩展建议如下：1） 激素原转化酶PC 2（SPC 2）和PC 3（SPC 3）的研究，包括其 生物合成、成熟和对激素原加工的作用 2）SPC 2基因缺失的影响 胰岛发育和形态的突变; 3） 基因调控及组织特异性转录的研究 编码SPC 2和SPC 3; 4）结构和功能研究 转化酶保守亚结构域的意义; 5）转化酶的研究 ProIGF-I在正常和转化细胞中的加工及其意义 6）羧肽酶E（CPE）缺乏对玉米幼苗生长的影响 胰岛激素原加工; 7）胰岛素受体的研究， 强调结合胞外域，并使用受体融合蛋白 研究其结构和生物合成; 8）进一步研究其结构和生物合成。 胰岛素和IGFs及其受体蛋白在低血糖中的演变 脊椎动物，重点是代谢和生长的分歧 胰岛素样肽（ILP）的调节功能， 原索动物

DESCRIPTION (Adapted from Applicant's Abstract): The major objective of this research program is to gain new insights into the molecular and cell biological mechanisms underlying the production and actions of insulin and related peptide hormones of the islets of Langerhans, including their genetic basis, evolutionary origins, and disorders in these processes which may contribute to the pathophysiology of diabetes and/or other diseases. New projects and extensions of previous work are proposed as follows: 1) Studies on prohormone convertases PC2 (SPC2) and PC3 (SPC3), including their biosynthesis, maturation and actions on prohormone processing in mice with targeted disruptions in their genes; 2) Effects of the SPC2 gene null mutation on the development and morphology of the islets of Langerhans; 3) studies on the regulation and tissue-specific transcription of the genes encoding SPC2 and SPC3; 4) Studies on the structure and functional significance of conserved subdomains of the convertases; 5) Studies on the processing of ProIGF-I and its significance in normal and transformed cell lines; 6) Studies on the effects of carboxypeptidase E (CPE) deficiency on islet prohormone processing; 7) Studies on the insulin receptor with emphasis on the binding ectodomain, and the use of receptor fusion proteins for studies of its structure and biosynthesis; 8) Further studies on the evolution of insulin and the IGFs and their receptor proteins in lower vertebrates, with emphasis on the divergence of metabolic and growth regulatory functions of a common ancestral insulin-like peptide (ILP) in protochordates.