Glucose induces expression of rat pyruvate carboxylase through a carbohydrate response element in the distal gene promoter

Biochem J. 2010 Feb 9;426(2):159-70. doi: 10.1042/BJ20091266.


Pyruvate carboxylase is an enzyme of the so-called pyruvate cycling pathways, which have been proposed to contribute to glucose-stimulated insulin secretion in pancreatic beta-cells. In the rat insulinoma cell line 832/13, transcripts from both the distal and proximal gene promoter for pyruvate carboxylase are up-regulated by glucose, with pyruvate carboxylase being expressed mainly from the distal gene promoter. At position -408 to -392 relative to the transcription start site, the distal gene promoter was found to contain a ChoRE (carbohydrate response element). Its deletion abolishes glucose responsiveness of the promoter, and the sequence can mediate glucose responsiveness to a heterologous gene promoter. ChREBP (carbohydrate response element-binding protein) and its dimerization partner Mlx (Max-like protein X) bind to the ChoRE in vitro. ChREBP further binds to the distal promoter region at a high glucose concentration in situ. The E-box-binding transcription factors USF1/2 (upstream stimulatory factor 1/2) and E2A variant 2 [also known as E47 and TCF3 (transcription factor 3)] can also bind to the ChoRE. Overexpression of E2A diminishes the magnitude of the glucose response from the pyruvate carboxylase ChoRE. This illustrates that competition between ChREBP-Mlx and other factors binding to the ChoRE affects glucose responsiveness. We conclude that a ChoRE in the distal gene promoter contributes to the glucose-mediated expression of pyruvate carboxylase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • Cell Line, Tumor
  • Gene Expression Regulation, Enzymologic*
  • Glucose / metabolism*
  • Molecular Sequence Data
  • Promoter Regions, Genetic*
  • Protein Binding
  • Pyruvate Carboxylase / blood
  • Pyruvate Carboxylase / chemistry
  • Pyruvate Carboxylase / genetics*
  • Pyruvate Carboxylase / metabolism
  • Rats / genetics*
  • Rats / metabolism
  • Response Elements*
  • Sequence Deletion
  • Transcriptional Activation


  • Pyruvate Carboxylase
  • Glucose