Green Janelle, Naot Dorit, Cooper Garth
M.E. Müller-Institute for Structural Biology, Biozentrum, University of Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland.
Biochem Biophys Res Commun. 2003 Oct 17;310(2):464-9. doi: 10.1016/j.bbrc.2003.09.046.
Maturity-onset diabetes of the young (MODY) is a monogenic subtype of Type 2 diabetes, defined as having an early age of onset, with a dominant inheritance pattern. Hepatocyte nuclear factor 1 (HNF1), which is encoded by the MODY3 gene, has been shown to bind the insulin promoter. Since the promoters of three pancreas-specific genes involved in glucose homeostasis-insulin, glucokinase, and amylin bind similar transcription factors, we were interested in whether HNF1 could also regulate amylin expression. In the present study, we used the electrophoretic mobility shift assay, to demonstrate that the HNF1 transcription factor can specifically bind to the amylin promoter. Moreover, co-transfection of an HNF1 expression vector with an amylin-CAT reporter plasmid decreased the activity of the amylin promoter by 85%. These data support the hypothesis that the amylin gene is regulated by HNF1 in a negative manner and may explain partially how HNF1 mutations result in diabetes.
青年发病的成年型糖尿病（MODY）是2型糖尿病的一种单基因亚型，其定义为发病年龄较早，呈显性遗传模式。由MODY3基因编码的肝细胞核因子1（HNF1）已被证明可结合胰岛素启动子。由于参与葡萄糖稳态的三个胰腺特异性基因——胰岛素、葡萄糖激酶和胰淀素的启动子结合相似的转录因子，我们感兴趣的是HNF1是否也能调节胰淀素的表达。在本研究中，我们使用电泳迁移率变动分析来证明HNF1转录因子可特异性结合胰淀素启动子。此外，将HNF1表达载体与胰淀素-CAT报告质粒共转染可使胰淀素启动子的活性降低85%。这些数据支持了胰淀素基因受HNF1负调控的假说，并可能部分解释HNF1突变如何导致糖尿病。
