Article

Regulation of hepatic gluconeogenesis by an ER-bound transcription factor, CREBH.

Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, 300 Chunchun-dong, Jangan-gu, Suwon, Gyeonggi-do 440-746, Korea.
Cell metabolism (impact factor: 17.35). 04/2010; 11(4):331-9. DOI:10.1016/j.cmet.2010.02.016 pp.331-9
Source: PubMed

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-1alpha-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.

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Keywords

active nuclear form
 
blood glucose levels
 
constitutively active CREBH activates transcription
 
CREBH
 
CREBH-N
 
Endoplasmic reticulum
 
enhancer site
 
fasting
 
hepatic gluconeogenesis
 
hepatic glucose metabolism
 
mammals
 
mice
 
PEPCK-C
 
PGC-1alpha-dependent manner
 
rodents
 
various metabolic pathways
 
well-characterized CREB/CRTC2 regulatory sequences