한빛사 논문
Abstract
Min-Woo Lee1, 9, Dipanjan Chanda2, 9, Jianqi Yang4, Hyunhee Oh5, Su Sung Kim5, Young-Sil Yoon1, Sungpyo Hong1, Keun-Gyu Park8, In-Kyu Lee7, Cheol Soo Choi5, 6, Richard W. Hanson4, Hueng-Sik Choi2, 3, and Seung-Hoi Koo1
1 Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, 300 Chunchun-dong, Jangan-gu, Suwon, Gyeonggi-do 440-746, Korea
2 Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju 500-757, Korea
3 Research Institute of Medical Sciences, Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju 501-746, Korea
4 Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH 44106-4935, USA
5 Lee Gil Ya Cancer and Diabetes Institute, Gil Medical Center, Gachon University of Medicine and Science, Incheon 405-760, Korea
6 Division of Endocrinology, Gil Medical Center, Gachon University of Medicine and Science, Incheon 405-760, Korea
7 Departments of Internal Medicine and Biochemistry and World Class University Program, Research Institute of Aging and Metabolism, Kyungpook National University School of Medicine, Daegu 700-422, Korea
8 Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
Summary
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
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