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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • 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 Date

  • September 13, 2001

Published In

Volume / Issue

  • 413 / 6852

Start / End Page

  • 131 - 138

PubMed ID

  • 11557972

Pubmed Central ID

  • 11557972

International Standard Serial Number (ISSN)

  • 0028-0836

Digital Object Identifier (DOI)

  • 10.1038/35093050

Language

  • eng

Conference Location

  • England