Studies on negative regulation of insulin gene expression in non-pancreatic cells

非胰腺细胞胰岛素基因表达负调控的研究

• 批准号: 01570636
• 负责人: TSUDA Kinsuke
• 金额: $ 1.28万
• 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: 1989
• 资助国家: 日本
• 起止时间: 1989 至 1990
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-01570636/
• 关键词: insulin gene; cyclic AMP; GLUT; 糖輸送担体(Glut); Glut 1; CAT アッセイ; Hep G2; HeLa; CAT活性; エンハンサ-領域; プロモ-タ-領域; cAMP

Insulin gene is expressed only in pancreatic B cells. So we have examined the effect of the 5'-branking region of the human insulin gene on its expression in non-pancreatic cells. The presence of the region containing the insulin gene enhancer (-339 to -169 bp) markedly repressed the promoter activity of the insulin gene. This suppressive phenomenon was restored by the addition of forsholin or dibutyryl cAMP suggesting that this region alone is not sufficient to repress completely insulin gene expression in the presence of extracellular stimuli which increase the intracellular cAMP level. These results show negative regulation of human insulin gene expression in non-pancreatu cells by these regions.In order to clarify whether glucose transporter (GLUT) is glucosensor of pancreatic B cells, we have also studied GLUT. We isolated RNA from rat islets of Langerhans and confirmed the presence of GLUT2 mRNA and GLUT1 mRNA. And we also demonstrated glucose regulates GLUT2 mRNA expression. These results suggest GLUT2 may be glucosensor of pancreatic B cells.By using Zucker fatty and Wistar fatty rats as models of obesity and diabetes, we showed that GLUT2 mRNA levels increase in both model rats and suggest that increassed GLUT2 mRNA levels may be associated with the development of obesity

胰岛素基因仅在胰腺B细胞中表达。因此，我们检测了人胰岛素基因的5 '分支区域对其在非胰腺细胞中表达的影响。含有胰岛素基因增强子的区域（-339至-169 bp）的存在显著抑制胰岛素基因的启动子活性。通过添加forsholin或二丁酰cAMP，这种抑制现象得以恢复，表明在增加细胞内cAMP水平的细胞外刺激存在下，该区域单独不足以完全抑制胰岛素基因表达。为了阐明葡萄糖转运蛋白（glucose transporter，GLUT）是否是胰腺B细胞的葡萄糖感受器，我们还对GLUT进行了研究。我们从大鼠胰岛中分离RNA，并证实GLUT 2 mRNA和GLUT 1 mRNA的存在。我们还证实了葡萄糖调节GLUT 2 mRNA的表达。本研究以Zucker肥胖大鼠和Wistar肥胖大鼠作为肥胖和糖尿病模型，发现两种模型大鼠的GLUT 2 mRNA水平均升高，提示GLUT 2 mRNA水平升高可能与肥胖的发生有关

项目成果

J. Takeda et al: "Negative regulation of human insulin gene expression by the 5'-flanking region in non-pancreatic cells." FEBS Letters. 247. 41-45 (1989)

J. Takeda 等人：“非胰腺细胞中 5 侧翼区域对人胰岛素基因表达的负调控。”

Y. Seino et al: "Expression of insulin and glucose transporter genes in obesity and diabetes" Progress in Obesity Ressarch. 371-374 (1990)

Y. Seino 等人：“肥胖和糖尿病中胰岛素和葡萄糖转运蛋白基因的表达”肥胖研究进展。

H.Yaro: "Tissue distribution and species difference of the brain type glucose transporter(GLUT3)" Biochem Biophys Res Commun. 174. 470-477 (1991)

H.Yaro：“脑型葡萄糖转运蛋白（GLUT3）的组织分布和物种差异”Biochem Biophys Res Commun。

Jun Takeda: "Negative regulation of human insulin gene expression by the 5′-flanking region in non-pancreatic cells" FEBS Letters. 247. 41-45 (1989)

Jun Takeda：“非胰腺细胞 5 侧翼区域对人胰岛素基因表达的负调节”FEBS Letters 247. 41-45 (1989)。

H. Yano et al: "Tissue distribution and speues difference of the brain type glucose transporter (GLUT3)" Biochem Biophys Res Commun. 174. 470-477 (1991)

H. Yano 等人：“脑型葡萄糖转运蛋白 (GLUT3) 的组织分布和喷射差异”Biochem Biophys Res Commun。