Regulation of Pacreatic β-cell Function by Transcription Factors.

转录因素在肺癌β-细胞的不同表型的发展、差异、再生和维护中发挥了重要作用。我们已经确定了一个完整的小鼠和人类PAX-4结构，这是一个扩展β-细胞开发的转录因子要素。我们还研究了乙型细胞核因子（HNF） -1α在β细胞中的作用。HNF-1 α基因导致MODY 3的突变，2型糖尿病的一个亚型。We overexpressed a dominant negative mutant of HNF-1？in MIN 6 cells and？zed insulin secretion in res\to various secretagogues。MIN 6细胞中HNF-1 α的抑制作用在胰岛素、葡萄糖和瘦素刺激性胰岛素保密作用下的严重潜在缺陷是接触。Our findings delineate the complex nature of-cell failure in MODY 3 patients。To investigate the mManagement isms regulating "\-cell mass"， we next studied the diseases causing changes in "\-cell mass"。沃尔夫拉姆综合症是一种罕见的自动疗法 ... More 正常恢复性紊乱特征是由糖尿病阳性、光学过敏、糖尿病insipidus和deafness。在病人中，泛肺性β-细胞被报告为选择性地丢失。我们有一个基因，命名为WFS 1，由位置克隆。基因编码是一种新型890氨基酸的跨膜蛋白，它与数据库中的任何蛋白质都不同源。初步数据建议WFS 1蛋白在内等离子体视网膜中存在，并在小鼠大脑中的神经元有限子集中表达。WFS 1蛋白质和机制的功能由哪些β-细胞在患者需要被澄清的情况下选择性地丢失。Persistent hyperinsulinemic hypoglycemia of infancy （PHHI） is a condition characterized by persistent insulin secretion in the presence of hypoglycemia。在一些患者与PHHI、β-cell超细胞、称为nesidioblastosis、在基因编码ATP敏感的土壤通道（Kyi D2 ATP Yye D2）中经常观察和变异。We identified three mutations in the SUR1 （one of two subunits of K-D2 ATP-D2） gene in Japanese patients with PHHI。根据体外功能研究，它被揭示了一个突变体（R1420 C）对腺苷核与SUR 1的不有效的协同结合。Less（低）

Transcription factors play important roles in the development, differentiation, regeneration and maintenance of the differentiated phenotype of pancreatic β-cells. We have determined a complete structure of mouse and human PAX-4, a transcription factor essential for the development of pancreatic β-cells. We also investigated the role of hepatocyte nuclear factor (HNF) -1α in the β-cells. Mutations of the HNF-1α gene cause MODY3, a subtype of type 2 diabetes. We overexpressed a dominant negative mutant of HNF-1α in MIN6 cells and analyzed insulin secretion in response to various secretagogues. Suppression of HNF-1α in MIN6 cells severely impaired potentiation of insulin secretion by arginine, whereas glucose- and leucine-stimulated insulin secretion was intact. Our findings delineate the complex nature of β-cell failure in MODY3 patients.To investigate the mechanisms regulating "β-cell mass", we next studied the diseases causing changes in "β-cell mass". Wolfram syndrome is a rare autos … More omal recessive disorder characterized by diabetes mellitus, optic atrophy, diabetes insipidus and deafness. In the patients, pancreatic β-cells are reported to be selectively lost. We have identified a gene, named WFS1, by positional cloning. The gene encodes a novel transmembrane protein of 890 amino acids, which is not homologous to any proteins in the database. Preliminary data suggest that WFS1 protein is in endoplasmic reticulum and expressed in limited subsets of neurons in mouse brain. Function of WFS1 protein and mechanisms by which β-cells are selectively lost in the patients need to be clarified. Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is a condition characterized by persistent insulin secretion in the presence of hypoglycemia. In some patients with PHHI, β-cell hyperplasia, called nesidioblastosis, is often observed and mutations were identified in the genes encoding ATP-sensitive potassium channel (KィイD2ATPィエD2). We identified three mutations in the SUR1 (one of two subunits of KィイD2ATPィエD2) gene in Japanese patients with PHHI. By in vitro functional studies, it was revealed that one of the mutations (R1420C) impaired cooperative binding of adenine nucleotides to SUR1. Less