SLC2A2 gene expression in kidney of diabetic rats is regulated by HNF-1α and HNF-3β

SLC2A2 gene expression in kidney of diabetic rats is regulated by HNF-1α and HNF-3β
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DOI:
10.1016/j.mce.2009.02.014
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发表时间:
2009-06-16
影响因子:
4.1
通讯作者:
Machado, U. F.
Machado, U. F.
中科院分区:
医学2区
文献类型:
--
作者:
Freitas, H. S.;Schaan, B. D.;Machado, U. F.

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我们推测,在糖尿病大鼠肾脏,肝细胞核因子(HNF-1 α。和HNF-3 β)在溶质载体2A 2(SLC 2A 2)基因的过表达中起关键作用。糖尿病大鼠提交或不提交快速(最多12小时)和短期(1,4和6天)胰岛素治疗进行了研究。在糖尿病患者中观察到GLUT 2 mRNA增加两倍,伴随着HNF-1 α和HNF-3 β表达和结合活性的显著增加。在12小时胰岛素处理大鼠中观察到GLUT 2 mRNA和HNF-3 β表达/活性额外增加2倍。6天胰岛素治疗使GLUT 2 mRNA和HNF-1 α表达和活性降低至非糖尿病大鼠的水平,而HNF-3 β降低至非胰岛素治疗的糖尿病大鼠的水平。我们的研究结果为糖尿病大鼠肾脏中SLC 2A 2基因的过表达与HNF-1 α和HNF-3 β的转录活性之间的联系提供了证据。此外,6天胰岛素治疗后SLC 2A 2基因的恢复也涉及HNF-1 α和HNF-3 β活性。(C)2009爱思唯尔爱尔兰有限公司保留所有权利。
We hypothesize that, in kidney of diabetic rats, hepatocyte nuclear factors (HNF-1 alpha. and HNF-3 beta) play a critical role in the overexpression of solute carrier 2A2 (SLC2A2) gene. Diabetic rats submitted or not to rapid (up to 12 h) and short-term (1, 4 and 6 days) insulin treatment were investigated. Twofold increase in GLUT2 mRNA was observed in diabetic, accompanied by significant increases in HNF-1 alpha and HNF-3 beta expression and binding activity. Additional 2-fold increase in GLUT2 mRNA and HNF-3 beta expression/activity was observed in 12-h insulin-treated rats. Six-day insulin treatment decreased GLUT2 mRNA and HNF-1 alpha expression and activity to levels of non-diabetic rats, whereas HNF-3 beta decreased to levels of non-insulin-treated diabetic rats. Our results provide evidence for a link between the overexpression of SLC2A2 gene and the transcriptional activity of HNF-1 alpha and HNF-3 beta in kidney of diabetic rats. Furthermore, recovery of SLC2A2 gene after 6-day insulin treatment also involves HNF-1 alpha and HNF-3 beta activity. (C) 2009 Elsevier Ireland Ltd. All rights reserved.