Regulation of Hepatic Gluconeogenesis by an ER-Bound Transcription Factor, CREBH

Min Woo Lee, Dipanjan Chanda, Jianqi Yang, Hyunhee Oh, Su Sung Kim, Young Sil Yoon, Sungpyo Hong, Keun Gyu Park, In Kyu Lee, Cheol Soo Choi, Richard W. Hanson, Hueng Sik Choi, Seung Hoi Koo

Research output: Contribution to journalArticle

130 Citations (Scopus)

Abstract

Endoplasmic reticulum (ER)-bound transcription factor families are shown to be involved in the control of various metabolic pathways. Here, we report a critical function of ER-bound transcription factor, CREBH, in the regulation of hepatic gluconeogenesis. Expression of CREBH is markedly induced by fasting or in the insulin-resistant state in rodents in a dexamethasone- and PGC-1α-dependent manner, which results in the accumulation of active nuclear form of CREBH (CREBH-N). Overexpression of constitutively active CREBH activates transcription of PEPCK-C or G6Pase by binding to its enhancer site that is distinct from the well-characterized CREB/CRTC2 regulatory sequences in vivo. Of interest, knockdown of CREBH in liver significantly reduces blood glucose levels without altering expression of genes involved in the ER stress signaling cascades in mice. These data suggest a crucial role for CREBH in the regulation of hepatic glucose metabolism in mammals.

Original languageEnglish
Pages (from-to)331-339
Number of pages9
JournalCell Metabolism
Volume11
Issue number4
DOIs
Publication statusPublished - 2010 Apr 7
Externally publishedYes

Keywords

  • HUMDISEASE

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Lee, M. W., Chanda, D., Yang, J., Oh, H., Kim, S. S., Yoon, Y. S., Hong, S., Park, K. G., Lee, I. K., Choi, C. S., Hanson, R. W., Choi, H. S., & Koo, S. H. (2010). Regulation of Hepatic Gluconeogenesis by an ER-Bound Transcription Factor, CREBH. Cell Metabolism, 11(4), 331-339. https://doi.org/10.1016/j.cmet.2010.02.016