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 3bp, 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 (-554bp/-538bp) is localized near the G-box (-543bp/-529bp). 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.