A crucial role of MafA as a novel therapeutic target for diabetes
A crucial role of MafA as a novel therapeutic target for diabetes
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DOI：
10.1074/jbc.m412013200
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发表时间：
2005-04-15
影响因子：
4.8
通讯作者：
Yamasaki, Y
中科院分区：
文献类型：
--
作者：
Kaneto, H;Matsuoka, T;Yamasaki, Y
MafA是最近分离的胰腺β细胞特异性转录因子，是胰岛素基因转录的有效激活因子。在这项研究中，我们发现MafA过表达，与PDX-1（胰腺和十二指肠同源盒因子-1）和NeuroD一起，显著增加肝脏中胰岛素基因的表达。因此，这种组合诱导了大量的胰岛素蛋白。此外，在链脲佐菌素诱导的糖尿病小鼠中，肝脏中MafA过表达与PDX-1和NeuroD一起显著改善了葡萄糖耐量，而PDX-1和NeuroD联合使用的效果要差得多。这些结果表明，MafA作为一种新的糖尿病治疗靶点具有重要作用。
MafA, a recently isolated pancreatic beta-cell-specific transcription factor, is a potent activator of insulin gene transcription. In this study, we show that MafA overexpression, together with PDX-1 ( pancreatic and duodenal homeobox factor-1) and NeuroD, markedly increases insulin gene expression in the liver. Consequently, substantial amounts of insulin protein were induced by such combination. Furthermore, in streptozotocin-induced diabetic mice, MafA overexpression in the liver, together with PDX-1 and NeuroD, dramatically ameliorated glucose tolerance, while combination of PDX-1 and NeuroD was much less effective. These results suggest a crucial role of MafA as a novel therapeutic target for diabetes.