Studies on the mechanism of transcription regulation of insulin gene in pancreatic B cell

胰腺B细胞胰岛素基因转录调控机制研究

• 批准号: 05670855
• 负责人: TSUDA Kinsuke
• 金额: $ 1.34万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05670855/
• 关键词: insulin gene; transcription; CRE (CAMP response element); CAMP; CRE(cyclic AMP response elenent); cAMP; CRE(cyclic AMP rospone element)

Diabetes mellitus is a disease of insulin deficiency. Insulin deficiency is caused by disturbances of insulin secretion and/or insulin action. The authors have published our data that suggest Japanese diabetic patients show hypoinsulinemia since early stage of diabetes mellitus. So to clarify the mechanism of insulin gene expression is very important. In this study we take the focus on the transcription of insulin gene because we have demonstrated that CREBP1 or c-Jun participate the insulin gene expression. We transfered the portion of DNA in the transcription region of human insulin gene into the fetal rat pancreatic beta cells and measured the transcription activities. We have the follwing results.1) One mechanism of insulin gene induction by glucose is caused through cAMP.2) The tanscription control of insulin gene by glucose have at least two mechanisms. One is related to CRE and one is not related to CRE.3) HIT-T15 cell (hamster pancreatic beta cell line) have disturbance of cAMP signal transduction.

糖尿病是一种胰岛素缺乏症。胰岛素缺乏症是由胰岛素分泌和/或胰岛素作用紊乱引起的。作者发表了我们的数据，表明日本糖尿病患者从糖尿病早期就表现出低胰岛素血症。因此，阐明胰岛素基因表达的调控机制具有重要意义。本研究的重点是胰岛素基因的转录，因为我们已经证明CREBP 1或c-Jun参与胰岛素基因的表达。将人胰岛素基因转录区的部分DNA导入胎鼠胰岛β细胞，测定其转录活性。结果表明：1）葡萄糖诱导胰岛素基因转录的机制之一是通过cAMP介导的; 2）葡萄糖对胰岛素基因转录的调控至少有两种机制。3）HIT-T15细胞（仓鼠胰腺β细胞系）存在cAMP信号转导障碍。