کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1930212 | 1050493 | 2012 | 6 صفحه PDF | دانلود رایگان |

The glucagon receptor (Gcgr) is essential for maintaining glucose homeostasis in the liver and for stimulating insulin secretion in pancreatic β-cells. Glucose induces rat Gcgr mRNA expression; however, the precise mechanism remains unknown. We previously have studied the role of the carbohydrate response element binding protein (ChREBP), a glucose-activated transcription factor, in the regulation of glucose-stimulated gene expression. The G-box has previously been reported to be responsible for glucose regulation of Gcgr mRNA expression. The G-box comprises two E-boxes separated by 3 bp, which distinguishes it from the carbohydrate response element (ChoRE), which has 5-bp spacing between the two E-boxes. In the rat Gcgr promoter, a putative ChoRE (−554 bp/−538 bp) is localized near the G-box (−543 bp/−529 bp). In rat INS-1E insulinoma cells, deletion studies of the rat Gcgr promoter show that ChoRE is a minimal glucose response element. Moreover, reporter assays using a pGL3 promoter vector, which harbors ChoRE and chromatin immunoprecipitation assays reveal that ChoRE is a functional glucose response element in the rat Gcgr promoter. Furthermore, In contrast, glucagon partly suppresses glucose-induced expression of Gcgr mRNA. Thus, ChREBP directly regulates rat Gcgr expression in INS-1E cells. In addition, negative feedback looping between ChREBP and GCGR may further contribute to the regulation of glucose-induced gene expression.
► ChREBP directly induces rat glucagon receptor (Gcgr) mRNA expression.
► ChoRE is a functional glucose response element in the rat Gcgr promoter.
► Glucagon partly suppresses glucose-induced expression of Gcgr mRNA.
► A closed loop between glucose and glucagon signals regulates Gcgr expression.
Journal: Biochemical and Biophysical Research Communications - Volume 417, Issue 4, 27 January 2012, Pages 1107–1112