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

Title
Regulation of Hepatic Gluconeogenesis by an ER-Bound Transcription Factor, CREBH
Authors
Min-Woo LeeDipanjan ChandaJianqi YangHyunhee OhSu Sung KimYoung-Sil YoonSungpyo HongKeun-Gyu ParkIn-Kyu LeeCheol Soo ChoiRichard W. HansonHueng-Sik ChoiSeung-Hoi Koo
Keimyung Author(s)
박근규
Department
Dept. of Internal Medicine (내과학)
Issue Date
2010
Publisher
School of Medicine
Citation
Cell metabolism, Vol.11(4) : 331-339, 2010
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. Highlights ► PGC-1α/GR activates CREBH expression under fasting or insulin-resistant conditions ► CREBH enhances hepatic gluconeogenesis via a CRTC2-dependent manner ► Depletion of CREBH in the liver ameliorates fasting hyperglycemia in diabetic mice Author Keywords HUMDISEASE
URI
http://www.cell.com/cell-metabolism/pdf/S1550-4131(10)00071-9.pdfhttp://kumel.medlib.dsmc.or.kr/handle/2015.oak/17040
ISSN
1550-4131
Appears in Collections:
1. 연구논문 > 1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
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