TY - JOUR
T1 - Rat glucagon receptor mRNA is directly regulated by glucose through transactivation of the carbohydrate response element binding protein
AU - Iizuka, Katsumi
AU - Tomita, Reiko
AU - Takeda, Jun
AU - Horikawa, Yukio
N1 - Funding Information:
This work was supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (K. Iizuka), the Kao Research Council for the Study of Healthcare Science (K. Iizuka), and in part by a New Energy and Industrial Technology Development Organization grant (Y. Horikawa).
PY - 2012/1/27
Y1 - 2012/1/27
N2 - 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.
AB - 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.
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U2 - 10.1016/j.bbrc.2011.12.042
DO - 10.1016/j.bbrc.2011.12.042
M3 - Article
C2 - 22198437
AN - SCOPUS:84856233779
VL - 417
SP - 1107
EP - 1112
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 4
ER -