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The promoter for the gene encoding the catalytic subunit of rat glucose-6-phosphatase contains two distinct glucose-responsive regions.

Publication ,  Journal Article
Pedersen, KB; Zhang, P; Doumen, C; Charbonnet, M; Lu, D; Newgard, CB; Haycock, JW; Lange, AJ; Scott, DK
Published in: Am J Physiol Endocrinol Metab
March 2007

Glucose homeostasis requires the proper expression and regulation of the catalytic subunit of glucose-6-phosphatase (G-6-Pase), which hydrolyzes glucose 6-phosphate to glucose in glucose-producing tissues. Glucose induces the expression of G-6-Pase at the transcriptional and posttranscriptional levels by unknown mechanisms. To better understand this metabolic regulation, we mapped the cis-regulatory elements conferring glucose responsiveness to the rat G-6-Pase gene promoter in glucose-responsive cell lines. The full-length (-4078/+64) promoter conferred a moderate glucose response to a reporter construct in HL1C rat hepatoma cells, which was dependent on coexpression of glucokinase. The same construct provided a robust glucose response in 832/13 INS-1 rat insulinoma cells, which are not glucogenic. Glucose also strongly increased endogenous G-6-Pase mRNA levels in 832/13 cells and in rat pancreatic islets, although the induced levels from islets were still markedly lower than in untreated primary hepatocytes. A distal promoter region was glucose responsive in 832/13 cells and contained a carbohydrate response element with two E-boxes separated by five base pairs. Carbohydrate response element-binding protein bound this region in a glucose-dependent manner in situ. A second, proximal promoter region was glucose responsive in both 832/13 and HL1C cells, with a hepatocyte nuclear factor 1 binding site and two cAMP response elements required for glucose responsiveness. Expression of dominant-negative versions of both cAMP response element-binding protein and CAAT/enhancer-binding protein blocked the glucose response of the proximal region in a dose-dependent manner. We conclude that multiple, distinct cis-regulatory promoter elements are involved in the glucose response of the rat G-6-Pase gene.

Duke Scholars

Published In

Am J Physiol Endocrinol Metab

DOI

ISSN

0193-1849

Publication Date

March 2007

Volume

292

Issue

3

Start / End Page

E788 / E801

Location

United States

Related Subject Headings

  • Transfection
  • Response Elements
  • Rats
  • Promoter Regions, Genetic
  • Molecular Sequence Data
  • Hepatocyte Nuclear Factor 1
  • Glucose-6-Phosphatase
  • Glucose
  • Genes, Reporter
  • Endocrinology & Metabolism
 

Citation

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Pedersen, K. B., Zhang, P., Doumen, C., Charbonnet, M., Lu, D., Newgard, C. B., … Scott, D. K. (2007). The promoter for the gene encoding the catalytic subunit of rat glucose-6-phosphatase contains two distinct glucose-responsive regions. Am J Physiol Endocrinol Metab, 292(3), E788–E801. https://doi.org/10.1152/ajpendo.00510.2006
Pedersen, Kim B., Pili Zhang, Chris Doumen, Marcel Charbonnet, Danhong Lu, Christopher B. Newgard, John W. Haycock, Alex J. Lange, and Donald K. Scott. “The promoter for the gene encoding the catalytic subunit of rat glucose-6-phosphatase contains two distinct glucose-responsive regions.Am J Physiol Endocrinol Metab 292, no. 3 (March 2007): E788–801. https://doi.org/10.1152/ajpendo.00510.2006.
Pedersen KB, Zhang P, Doumen C, Charbonnet M, Lu D, Newgard CB, et al. The promoter for the gene encoding the catalytic subunit of rat glucose-6-phosphatase contains two distinct glucose-responsive regions. Am J Physiol Endocrinol Metab. 2007 Mar;292(3):E788–801.
Pedersen, Kim B., et al. “The promoter for the gene encoding the catalytic subunit of rat glucose-6-phosphatase contains two distinct glucose-responsive regions.Am J Physiol Endocrinol Metab, vol. 292, no. 3, Mar. 2007, pp. E788–801. Pubmed, doi:10.1152/ajpendo.00510.2006.
Pedersen KB, Zhang P, Doumen C, Charbonnet M, Lu D, Newgard CB, Haycock JW, Lange AJ, Scott DK. The promoter for the gene encoding the catalytic subunit of rat glucose-6-phosphatase contains two distinct glucose-responsive regions. Am J Physiol Endocrinol Metab. 2007 Mar;292(3):E788–E801.

Published In

Am J Physiol Endocrinol Metab

DOI

ISSN

0193-1849

Publication Date

March 2007

Volume

292

Issue

3

Start / End Page

E788 / E801

Location

United States

Related Subject Headings

  • Transfection
  • Response Elements
  • Rats
  • Promoter Regions, Genetic
  • Molecular Sequence Data
  • Hepatocyte Nuclear Factor 1
  • Glucose-6-Phosphatase
  • Glucose
  • Genes, Reporter
  • Endocrinology & Metabolism