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Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1.

Publication ,  Journal Article
Yoon, JC; Puigserver, P; Chen, G; Donovan, J; Wu, Z; Rhee, J; Adelmant, G; Stafford, J; Kahn, CR; Granner, DK; Newgard, CB; Spiegelman, BM
Published in: Nature
September 13, 2001

Blood glucose levels are maintained by the balance between glucose uptake by peripheral tissues and glucose secretion by the liver. Gluconeogenesis is strongly stimulated during fasting and is aberrantly activated in diabetes mellitus. Here we show that the transcriptional coactivator PGC-1 is strongly induced in liver in fasting mice and in three mouse models of insulin action deficiency: streptozotocin-induced diabetes, ob/ob genotype and liver insulin-receptor knockout. PGC-1 is induced synergistically in primary liver cultures by cyclic AMP and glucocorticoids. Adenoviral-mediated expression of PGC-1 in hepatocytes in culture or in vivo strongly activates an entire programme of key gluconeogenic enzymes, including phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase, leading to increased glucose output. Full transcriptional activation of the PEPCK promoter requires coactivation of the glucocorticoid receptor and the liver-enriched transcription factor HNF-4alpha (hepatic nuclear factor-4alpha) by PGC-1. These results implicate PGC-1 as a key modulator of hepatic gluconeogenesis and as a central target of the insulin-cAMP axis in liver.

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Published In

Nature

DOI

ISSN

0028-0836

Publication Date

September 13, 2001

Volume

413

Issue

6852

Start / End Page

131 / 138

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • Transcription Factors
  • Response Elements
  • Receptors, Glucocorticoid
  • Receptor, Insulin
  • Rats, Wistar
  • Rats
  • RNA, Messenger
  • Phosphoproteins
  • Phosphoenolpyruvate Carboxykinase (GTP)
 

Citation

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Yoon, J. C., Puigserver, P., Chen, G., Donovan, J., Wu, Z., Rhee, J., … Spiegelman, B. M. (2001). Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1. Nature, 413(6852), 131–138. https://doi.org/10.1038/35093050
Yoon, J. C., P. Puigserver, G. Chen, J. Donovan, Z. Wu, J. Rhee, G. Adelmant, et al. “Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1.Nature 413, no. 6852 (September 13, 2001): 131–38. https://doi.org/10.1038/35093050.
Yoon JC, Puigserver P, Chen G, Donovan J, Wu Z, Rhee J, et al. Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1. Nature. 2001 Sep 13;413(6852):131–8.
Yoon, J. C., et al. “Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1.Nature, vol. 413, no. 6852, Sept. 2001, pp. 131–38. Pubmed, doi:10.1038/35093050.
Yoon JC, Puigserver P, Chen G, Donovan J, Wu Z, Rhee J, Adelmant G, Stafford J, Kahn CR, Granner DK, Newgard CB, Spiegelman BM. Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1. Nature. 2001 Sep 13;413(6852):131–138.
Journal cover image

Published In

Nature

DOI

ISSN

0028-0836

Publication Date

September 13, 2001

Volume

413

Issue

6852

Start / End Page

131 / 138

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • Transcription Factors
  • Response Elements
  • Receptors, Glucocorticoid
  • Receptor, Insulin
  • Rats, Wistar
  • Rats
  • RNA, Messenger
  • Phosphoproteins
  • Phosphoenolpyruvate Carboxykinase (GTP)