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Studies on molecular mechanism of etiology of diabetes mellitus

糖尿病病因分子机制研究

基本信息

批准号：
02671093
负责人：
SEINO Yutaka
金额：
$ 1.41万
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：
1990
资助国家：
日本
起止时间：
1990 至 1991
项目状态：
已结题

项目摘要

In order to investigate the regulation of glucose transporter gene expression in the altered metabolic conditions of diabetes, we have measured MRNA levels encoding GLUT4 in the liver and GLUT4 in the gastrocnemius muscle from various insulin resistant animal models, including Zucker fatty, Wistar fatty, and streptozocin(STZ)-treated diabetic rats. Northern blot analysis revealed that GLUT2 MRNA levels were significantly(P<0.001)elevated in 14 wk Zucker fatty and Wistar fatty rats relative to lean littermates but were similar in these two groups at 5 wk of age. Furthermore, there was significant increase(P<0.01)in GLUT2 MRNA levels in STZ diabetic rats at 3 wk after treatment. GLUT4 MRNA levels were not significantly different between control and insulin resistant rats in all animal models. These results indicate that neither hyperinsulinemia nor hyperglycemia affects GLUT4 MRNA levels in the muscle. However, GLUT2 MRNA levels in the liver were elevated in obesity and diabetes, althoug … More h this regulatory event occurred independently from circulating insulin or glucose concentrations. On the other hand, previous studies revealed that rat islets express the GLUT2-liver facilitative glucose transporter isoform, a glucose carrier with a low affinity for glucose but a high capacity for glucose transport. These studies indicated the presence of a second glucose transporter in rat islets ; however, they did not indicate to which of the five known facilitative glucose transporters it corresponded. In this study, we isolated RNA from rat islets of Langerhans and confirmed the presence of GLUT2 MRNA. In addition, we present data indicating that the second isoform expressed in islets is the GLUTI-erythrocyte isoform. The effect of culturing islets in 5.5, 8.3 or 11.1 mM glucose on the levels of GLUT1 and GLUT2 MRNA also was examined. The levels of GLUTI and GLUT2 MRNA were two- and threefold higher, respectively, in islets cultured for 24 h in 11.1 mM glucose compared with those incubated in the presence of 5.5 mM glucose. Therefore, the previously observed increase in GLUT2 MRNA levels in the islets of rats made hyperglycemic by chronic infusion of glucose can be mimicked in vitro, implying that glucose regulates GLUT2 MRNA expression. Less

为了研究葡萄糖转运蛋白基因表达的调节在糖尿病的代谢条件改变，我们已经测量了mRNA水平编码GLUT 4在肝脏和GLUT 4在腓肠肌从各种胰岛素抵抗的动物模型，包括Zucker脂肪，Wistar脂肪，和链脲佐菌素（STZ）治疗的糖尿病大鼠。北方印迹分析显示，14周龄Zucker脂肪大鼠和Wistar脂肪大鼠的GLUT 2 mRNA水平显著（P<0.001）升高，但在5周龄时这两组相似。STZ糖尿病大鼠GLUT 2 mRNA水平在治疗后3 wk显著升高（P<0.01）。在所有动物模型中，对照组和胰岛素抵抗大鼠之间的GLUT 4 mRNA水平无显著差异。这些结果表明，高胰岛素血症和高血糖症都不会影响肌肉中的GLUT 4 mRNA水平。然而，尽管肥胖和糖尿病患者肝脏中的GLUT 2 mRNA水平升高， ...更多信息 h该调节事件的发生与循环胰岛素或葡萄糖浓度无关。另一方面，先前的研究表明，大鼠胰岛表达GLUT 2-肝脏促进葡萄糖转运蛋白亚型，一种对葡萄糖亲和力低但葡萄糖转运能力高的葡萄糖载体。这些研究表明大鼠胰岛中存在第二种葡萄糖转运蛋白;然而，他们没有指出它对应于五种已知的促进性葡萄糖转运蛋白中的哪一种。在这项研究中，我们从大鼠胰岛中分离出RNA，并证实了GLUT 2 mRNA的存在。此外，我们目前的数据表明，在胰岛中表达的第二种亚型是GLUTI-红细胞亚型。还检查了在5.5、8.3或11.1 mM葡萄糖中培养胰岛对GLUT 1和GLUT 2 mRNA水平的影响。在11.1 mM葡萄糖中培养24 h的胰岛中，GLUTI和GLUT 2 mRNA的水平分别比在5.5 mM葡萄糖存在下培养的胰岛高2倍和3倍。因此，先前观察到的大鼠胰岛中GLUT 2 mRNA水平的增加通过长期输注葡萄糖而产生高血糖，可以在体外模拟，这意味着葡萄糖调节GLUT 2 mRNA的表达。少