Translational control of glucose-induced insulin biosynthesis

葡萄糖诱导的胰岛素生物合成的转化控制

• 批准号: 23659161
• 负责人: TAKASAWA Shin
• 金额: $ 2.41万
• 依托单位: Nara Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23659161/
• 关键词: インスリン; 翻訳調節; 糖尿病; インスリン遺伝子; ブドウ糖; 膵β細胞

Glucose-induced insulin synthesis is important for homeostasis of blood glucose level and regulated by transcription, translation, and secretion. In the present study, we fused several lengths of 5’-untranslated region of human insulin mRNA with protein-destabilization sequence (PEST sequence). We then introduced the fused genes into glucose-sensitive human insulin producing cells (1.1B4 cells) and determined mRNA sequence essential for glucose-induced pro-insulin synthesis by translation. The sequence “GUCCUUCUG” in the 5’-untranslated region of human insulin mRNA was indicated as a sequence essential for translational control of glucose-induced pro-insulin synthesis. The human (Homo sapiens sapiens) sequence was highly conserved in chimpanzee (Pan troglodytes), rat (Rattus norvegicus), mouse (Mus musculus), guinea pig (Cavia Porcellus), pig (Sus scrofa domesticus), bovine(Bos taurus), chicken (Gallus gallus domesticus), leopard frog (Rena pipiens), and zebrafish (Danio rerio) insulin mRNAs; The sequence “NYNSYYNR “ was suggested as consensus sequence for glucose-induced translational control of insulin biosynthesis.

葡萄糖诱导的胰岛素合成对于血糖水平的稳态是重要的，并且受到转录、翻译和分泌的调节。在本研究中，我们融合了几个长度的人胰岛素mRNA的5 '-非翻译区与蛋白质去稳定序列（PEST序列）。然后，我们将融合基因导入葡萄糖敏感的人胰岛素产生细胞（1.1B4细胞），并通过翻译确定葡萄糖诱导的胰岛素原合成所必需的mRNA序列。人胰岛素mRNA的5 '-非翻译区中的序列“GUCCUUCUG”被指示为葡萄糖诱导的胰岛素原合成的翻译控制所必需的序列。人类（智人）序列在黑猩猩中高度保守（黑猩猩），大鼠（褐家鼠），小鼠（Mus musculus），豚鼠（豚鼠），猪（野猪），牛（牛金牛），鸡（原鸡），豹蛙（雷纳pipiens）和斑马鱼（Danio rerio）胰岛素mRNA;序列“NYNSYYNR“被认为是葡萄糖诱导的胰岛素生物合成的翻译控制的共有序列。

项目成果

Dysfunction and proliferation of pancreatic beta cells by intermittent hypoxia.

间歇性缺氧导致胰腺β细胞功能障碍和增殖。

• 发表时间: 2013
• 作者: Ota H;Itaya-Hironaka A;Yamauchi A;Sakuramoto-Tsuchida S;Takeda M;Fujimura T;Tsujinaka H;Tsuchida C;Tamaki S;Takasawa S;Kimura H.
• 通讯作者: Kimura H.

REG family genes expression in lung cancer

REG家族基因在肺癌中的表达

• 发表时间: 2011
• 作者: Naito;H.;Tojo;T.;Kimura;M.;Kawaguchi;T.;Takasawa;S.;Itaya-Hironaka;A.;Dohi;Y. and Taniguchi;S
• 通讯作者: S

Intermittent hypoxia induces rat smooth muscle cell proliferation with upregulation of erbB2 receptor and epidermal growth factor family mRNAs

间歇性缺氧诱导大鼠平滑肌细胞增殖，上调 erbB2 受体和表皮生长因子家族 mRNA

• 发表时间: 2011
• 作者: 京谷陽司;高沢 伸;太田浩世;広中安佐子;山内晶世;土田澄代;木村 弘;宇野雅之;吉栖正典
• 通讯作者: 吉栖正典

Biomarkers for diagnosis and monitoring of Celiac disease.

用于诊断和监测乳糜泻的生物标志物。

• DOI: 10.1097/mcg.0b013e31827874e3
• 发表时间: 2013
• 期刊: J. Clin. Gastroenterol.
• 作者: Vives-Pi;M.
• 通讯作者: M.

Attenuation of glucose-induced insulin secretion from pancreatic beta cells by intermittent hypoxia via down-regulation of CD38.

通过下调 CD38，间歇性缺氧可减弱葡萄糖诱导的胰腺 β 细胞的胰岛素分泌。

• 发表时间: 2011
• 期刊: Diabetologia
• 影响因子: 8.2
• 作者: Ota;H.;Tamaki;S.;Itaya-Hironaka;A.;Yamauchi;A.;Sakuramoto-Tsuchida;S.;Morioka;T.;Takasawa;S. and Kimura;H.
• 通讯作者: H.