FUNCTION OF NOVEL GENE (BRG1) EXPRESSED IN PANCREATIC BETA CELLS AND IMPLICATION IN PATHOGENESIS OF DIABETES.

胰腺β细胞中表达的新基因（BRG1）的功能及其在糖尿病发病机制中的意义。

基本信息

批准号：
14571102
负责人：
HAMAGUCHI Kazuyuki
金额：
$ 2.18万
依托单位：
Oita University (2004)大分医科大学 (2002-2003)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

Complementary DNA of BRG1 (β related gene 1) has been isolated from the mouse pancreatic β cell-line (MIN6) which shows high level of BRG1 expression. In the research theme-1, rabbit polyclonal antibody against synthetic BRG1 peptides was obtained. Using this antibody, we examined the cellular localization of BRG1 protein in the pancreatic islet of mouse model for type 2 diabetes, db/db. Light-microscopic immunofluorescent staining for BRG1 protein revealed the cellular topography in the pancreatic a cells but not β, δ, or PP cells. Other non-endocrine tissues, i.e., liver and kidney, did not show any staining for BRG1 antibody. Immunoelectron microscopy revealed that the co-localization of BRG1 protein in the glucagon-granule in the pancreatic a cells. We assume that the pancreatic β cell line may de-differentiate to express protein which is normally expressed in the pancreatic α cells. BRG1 may be a unique protein which is colocalized in the glucagon granule of pancreatic α cells.In … More the research theme-2 and theme-3, we carried out the genetic analysis of the genes which are etiologically related to diabetes. We obtained the genomic DNA samples from type 1 diabetic patients, GAD antibody-positive or negative type 2 diabetic patients, and normal control subjects. In the research theme-2, we investigated polymorphisms of inhibitor of κB-like (IKBL ; also known as"NFKBIL1") gene which is reported the association to cellular apoptosis and locates in the class III region of HLA complex. The results indicated a possible independent association between type 1 diabetes and SNPs in the promoter of the IKBL gene. In the research theme-3, we conducted to clarify the clinical and genetic characteristics of the diabetic patients who have antibodies to glutamic acid decarboxylase (GADab) but are diagnosed initially as type 2 diabetes because of the slow progression. The data indicated that patients with a high-GADab titer share the autoimmune background characteristic of type 1 diabetes. Less

BRG1（β相关基因1）的互补DNA已从显示高水平BRG1表达的小鼠胰腺β细胞系（MIN6）中分离出来。在研究主题-1中，使用抗合成BRG1肽获得了兔多克隆抗体。利用该抗体，我们通过光镜免疫荧光染色检查了 2 型糖尿病小鼠模型胰岛中 BRG1 蛋白的细胞定位。 BRG1 蛋白显示了胰腺 α 细胞中的细胞形态，但未显示出 β、δ 或 PP 细胞中的细胞拓扑结构。其他非内分泌组织（即肝脏和肾脏）没有显示出任何 BRG1 抗体的染色结果。我们假设胰腺β细胞系可能去分化以表达通常在胰高血糖素颗粒中表达的蛋白质。 BRG1可能是一种独特的蛋白质，共定位于胰腺α细胞的胰高血糖素颗粒中。在研究主题2和主题3中，我们对与糖尿病病因相关的基因进行了遗传分析。我们从1型糖尿病患者、GAD抗体阳性或阴性2型糖尿病患者以及正常对照受试者中获取了基因组DNA样本。在研究主题2中，我们研究了抑制剂的多态性。据报道，κB样(IKBL；也称为“NFKBIL1”)基因与细胞凋亡相关并且位于HLA复合物的III类区域。结果表明1型糖尿病与启动子中的SNP之间可能存在独立关联。在研究主题3中，我们旨在阐明具有谷氨酸脱羧酶（GADab）抗体但最初被诊断为2型糖尿病的糖尿病患者的临床和遗传特征。由于进展缓慢，数据表明 GADab 滴度高的患者具有 1 型糖尿病的自身免疫背景特征。