期刊
BMB REPORTS
卷 46, 期 12, 页码 567-574出版社
KOREAN SOCIETY BIOCHEMISTRY & MOLECULAR BIOLOGY
DOI: 10.5483/BMBRep.2013.46.12.248
关键词
CREB; FoxO1; Gluconeogenesis; Liver; Transcription
资金
- National Research Foundation of Korea (NRF)
- Ministry of Education, Science and Technology, Republic of Korea [NRF-2010-0015098, NRF-2012M3A9B6055345]
- Korean Health Technology RD Project
- Ministry of Health & Welfare, Republic of Korea [HI13C1886]
Liver plays a major role in maintaining glucose homeostasis in mammals. Under fasting conditions, hepatic glucose production is critical as a source of fuel to maintain the basic functions in other tissues, including skeletal muscle, red blood cells, and the brain. Fasting hormones glucagon and cortisol play major roles during the process, in part by activating the transcription of key enzyme genes in the gluconeogenesis such as phosphoenol pyruvate carboxykinase (PEPCK) and glucose 6 phosphatase catalytic subunit (G6Pase). Conversely, gluconeogenic transcription is repressed by pancreatic insulin under feeding conditions, which effectively inhibits transcriptional activator complexes by either promoting post-translational modifications or activating transcriptional inhibitors in the liver, resulting in the reduction of hepatic glucose output. The transcriptional regulatory machineries have been highlighted as targets for type 2 diabetes drugs to control glycemia, so understanding of the complex regulatory mechanisms for transcription circuits for hepatic gluconeogenesis is critical in the potential development of therapeutic tools for the treatment of this disease. In this review, the current understanding regarding the roles of two key transcriptional activators, CREB and FoxO1, in the regulation of hepatic gluconeogenic program is discussed.
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