title: Regulation of hepatic gluconeogenesis by an ER-bound transcription factor, CREBH.
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.
authors.affiliation: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, 300 Chunchun-dong, Jangan-gu, Suwon, Gyeonggi-do 440-746, Korea.
authors.forename: Min-Woo
authors.initials: MW
authors.lastname: Lee
authors.forename: Dipanjan
authors.initials: D
authors.lastname: Chanda
authors.forename: Jianqi
authors.initials: J
authors.lastname: Yang
authors.forename: Hyunhee
authors.initials: H
authors.lastname: Oh
authors.forename: Su Sung
authors.initials: SS
authors.lastname: Kim
authors.forename: Young-Sil
authors.initials: YS
authors.lastname: Yoon
authors.forename: Sungpyo
authors.initials: S
authors.lastname: Hong
authors.forename: Keun-Gyu
authors.initials: KG
authors.lastname: Park
authors.forename: In-Kyu
authors.initials: IK
authors.lastname: Lee
authors.forename: Cheol Soo
authors.initials: CS
authors.lastname: Choi
authors.forename: Richard W
authors.initials: RW
authors.lastname: Hanson
authors.forename: Hueng-Sik
authors.initials: HS
authors.lastname: Choi
authors.forename: Seung-Hoi
authors.initials: SH
authors.lastname: Koo
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D005943:Gluconeogenesis / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D015534:Trans-Activators / Q000494:pharmacology; D014157:Transcription Factors
chemical_list: D001786:Blood Glucose; C500051:Creb3l3 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D003907:Dexamethasone