MafA is a key regulator of glucose-stimulated insulin secretion
MafA is a key regulator of glucose-stimulated insulin secretion
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DOI：
10.1128/mcb.25.12.4969-4976.2005
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发表时间：
2005-06-01
影响因子：
5.3
通讯作者：
Takahashi, S
中科院分区：
文献类型：
--
作者：
Zhang, C;Moriguchi, T;Takahashi, S
MafA是一种转录因子，与胰岛素基因的启动子结合，并被认为可响应血清葡萄糖水平调节胰岛素转录，但目前尚无体内证据支持这一假设。为了分析MafA在体内胰岛素转录和葡萄糖稳态中的作用，我们产生MafA缺陷小鼠。在这里，我们报告MafA突变小鼠显示不耐受葡萄糖和发展糖尿病。详细的分析表明，葡萄糖，精氨酸，或氯化钾刺激的胰腺β细胞的胰岛素分泌严重受损，虽然胰岛素含量本身没有显着影响。MafA缺陷小鼠也显示出年龄依赖性胰岛异常。进一步的分析显示，胰岛素1，胰岛素2，Pdx 1，β 2和Glut-2转录物在MafA缺陷小鼠中减少。这些结果表明，MalfA是体内葡萄糖刺激的胰岛素分泌的关键调节剂。
MafA is a transcription factor that binds to the promoter in the insulin gene and has been postulated to regulate insulin transcription in response to serum glucose levels, but there is no current in vivo evidence to support this hypothesis. To analyze the role of MafA in insulin transcription and glucose homeostasis in vivo, we generated MafA-deficient mice. Here we report that MafA mutant mice display intolerance to glucose and develop diabetes mellitus. Detailed analyses revealed that glucose-, arginine-, or KCl-stimulated insulin secretion from pancreatic beta cells is severely impaired, although insulin content per se is not significantly affected. MafA-deficient mice also display age-dependent pancreatic islet abnormalities. Further analysis revealed that insulin 1, insulin 2, Pdx1, Beta2, and Glut-2 transcripts are diminished in MafA-deficient mice. These results show that MalfA is a key regulator of glucose-stimulated insulin secretion in vivo.