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Absence of the SRC-2 coactivator results in a glycogenopathy resembling Von Gierke's disease.

Publication ,  Journal Article
Chopra, AR; Louet, J-F; Saha, P; An, J; Demayo, F; Xu, J; York, B; Karpen, S; Finegold, M; Moore, D; Chan, L; Newgard, CB; O'Malley, BW
Published in: Science
November 28, 2008

Hepatic glucose production is critical for basal brain function and survival when dietary glucose is unavailable. Glucose-6-phosphatase (G6Pase) is an essential, rate-limiting enzyme that serves as a terminal gatekeeper for hepatic glucose release into the plasma. Mutations in G6Pase result in Von Gierke's disease (glycogen storage disease-1a), a potentially fatal genetic disorder. We have identified the transcriptional coactivator SRC-2 as a regulator of fasting hepatic glucose release, a function that SRC-2 performs by controlling the expression of hepatic G6Pase. SRC-2 modulates G6Pase expression directly by acting as a coactivator with the orphan nuclear receptor RORalpha. In addition, SRC-2 ablation, in both a whole-body and liver-specific manner, resulted in a Von Gierke's disease phenotype in mice. Our results position SRC-2 as a critical regulator of mammalian glucose production.

Duke Scholars

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Published In

Science

DOI

EISSN

1095-9203

Publication Date

November 28, 2008

Volume

322

Issue

5906

Start / End Page

1395 / 1399

Location

United States

Related Subject Headings

  • Triglycerides
  • Transcription, Genetic
  • Retinoic Acid Receptor alpha
  • Response Elements
  • Receptors, Retinoic Acid
  • RNA Interference
  • Nuclear Receptor Coactivator 2
  • Mice, Knockout
  • Mice
  • Male
 

Citation

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Chopra, A. R., Louet, J.-F., Saha, P., An, J., Demayo, F., Xu, J., … O’Malley, B. W. (2008). Absence of the SRC-2 coactivator results in a glycogenopathy resembling Von Gierke's disease. Science, 322(5906), 1395–1399. https://doi.org/10.1126/science.1164847
Chopra, Atul R., Jean-Francois Louet, Pradip Saha, Jie An, Franco Demayo, Jianming Xu, Brian York, et al. “Absence of the SRC-2 coactivator results in a glycogenopathy resembling Von Gierke's disease.Science 322, no. 5906 (November 28, 2008): 1395–99. https://doi.org/10.1126/science.1164847.
Chopra AR, Louet J-F, Saha P, An J, Demayo F, Xu J, et al. Absence of the SRC-2 coactivator results in a glycogenopathy resembling Von Gierke's disease. Science. 2008 Nov 28;322(5906):1395–9.
Chopra, Atul R., et al. “Absence of the SRC-2 coactivator results in a glycogenopathy resembling Von Gierke's disease.Science, vol. 322, no. 5906, Nov. 2008, pp. 1395–99. Pubmed, doi:10.1126/science.1164847.
Chopra AR, Louet J-F, Saha P, An J, Demayo F, Xu J, York B, Karpen S, Finegold M, Moore D, Chan L, Newgard CB, O’Malley BW. Absence of the SRC-2 coactivator results in a glycogenopathy resembling Von Gierke's disease. Science. 2008 Nov 28;322(5906):1395–1399.
Journal cover image

Published In

Science

DOI

EISSN

1095-9203

Publication Date

November 28, 2008

Volume

322

Issue

5906

Start / End Page

1395 / 1399

Location

United States

Related Subject Headings

  • Triglycerides
  • Transcription, Genetic
  • Retinoic Acid Receptor alpha
  • Response Elements
  • Receptors, Retinoic Acid
  • RNA Interference
  • Nuclear Receptor Coactivator 2
  • Mice, Knockout
  • Mice
  • Male