Rat glucagon receptor mRNA is directly regulated by glucose through transactivation of the carbohydrate response element binding protein

Katsumi Iizuka, Reiko Tomita, Jun Takeda, Yukio Horikawa

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1107-1112
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume417
Issue number4
DOIs
Publication statusPublished - 27-01-2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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