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Stimulation of glucose-6-phosphatase gene expression by glucose and fructose-2,6-bisphosphate.

Publication ,  Journal Article
Argaud, D; Kirby, TL; Newgard, CB; Lange, AJ
Published in: J Biol Chem
May 9, 1997

Glucose-6-phosphatase, a key enzyme in the homeostatic regulation of blood glucose concentration, catalyzes the terminal step in gluconeogenesis and glycogenolysis. Glucose, the product of the glucose-6-phosphatase reaction, dramatically increases the level of glucose-6-phosphatase mRNA transcripts in primary hepatocytes (20-fold), and the maximum response is obtained at a glucose concentration as low as 11 mM. Glucose specifically increases glucose-6-phosphatase mRNA and L-type pyruvate kinase mRNA. In the rat hepatoma-derived cell line, Fao, glucose increases the glucose-6-phosphatase mRNA only modestly (3-fold). In the presence of high glucose concentrations, overexpression of glucokinase in Fao cells via recombinant adenovirus vectors increases lactate production to the level found in primary hepatocytes and increases glucose-6-phosphatase gene expression by 21-fold. Similar overexpression of hexokinase I in Fao cells with high levels of glucose does not increase lactate production nor does it change the response of glucose-6-phosphatase mRNA to glucose. Glucokinase overexpression in Fao cells blunts the previously reported inhibitory effect of insulin on glucose-6-phosphatase gene expression in these cells. Raising the cellular concentration of fructose-2,6-bisphosphate, a potent effector of the direction of carbon flux through the gluconeogenic and glycolytic pathways, also stimulated glucose-6-phosphatase gene expression in Fao cells. Increasing the fructose-2,6-bisphosphate concentration over a 15-fold range (12 +/- 1 to 187 +/- 17 pmol/plate) via an adenoviral vector overexpression system, led to a 6-fold increase (0.32 +/- 0. 03 to 2.2 +/- 0.33 arbitrary units of mRNA) in glucose-6-phosphatase gene expression with a concomitant increase in glycolysis and a decrease in gluconeogenesis. Also, the effects of fructose-2, 6-bisphosphate concentrations on fructose-1,6-bisphosphatase gene expression were stimulatory, leading to a 5-6-fold increase in mRNA level over a 15-fold range in fructose-2,6-bisphosphate level. Liver pyruvate kinase and phosphoenolpyruvate carboxykinase mRNA were unchanged by the manipulation of fructose-2,6-bisphosphate level.

Duke Scholars

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

May 9, 1997

Volume

272

Issue

19

Start / End Page

12854 / 12861

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Rats
  • RNA, Messenger
  • Liver
  • Kinetics
  • Glucose-6-Phosphatase
  • Glucose
  • Glucokinase
  • Gene Expression Regulation, Enzymologic
  • Fructosediphosphates
 

Citation

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Argaud, D., Kirby, T. L., Newgard, C. B., & Lange, A. J. (1997). Stimulation of glucose-6-phosphatase gene expression by glucose and fructose-2,6-bisphosphate. J Biol Chem, 272(19), 12854–12861. https://doi.org/10.1074/jbc.272.19.12854
Argaud, D., T. L. Kirby, C. B. Newgard, and A. J. Lange. “Stimulation of glucose-6-phosphatase gene expression by glucose and fructose-2,6-bisphosphate.J Biol Chem 272, no. 19 (May 9, 1997): 12854–61. https://doi.org/10.1074/jbc.272.19.12854.
Argaud D, Kirby TL, Newgard CB, Lange AJ. Stimulation of glucose-6-phosphatase gene expression by glucose and fructose-2,6-bisphosphate. J Biol Chem. 1997 May 9;272(19):12854–61.
Argaud, D., et al. “Stimulation of glucose-6-phosphatase gene expression by glucose and fructose-2,6-bisphosphate.J Biol Chem, vol. 272, no. 19, May 1997, pp. 12854–61. Pubmed, doi:10.1074/jbc.272.19.12854.
Argaud D, Kirby TL, Newgard CB, Lange AJ. Stimulation of glucose-6-phosphatase gene expression by glucose and fructose-2,6-bisphosphate. J Biol Chem. 1997 May 9;272(19):12854–12861.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

May 9, 1997

Volume

272

Issue

19

Start / End Page

12854 / 12861

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Rats
  • RNA, Messenger
  • Liver
  • Kinetics
  • Glucose-6-Phosphatase
  • Glucose
  • Glucokinase
  • Gene Expression Regulation, Enzymologic
  • Fructosediphosphates