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Transcriptional regulators of hepatic gluconeogenesis

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Abstract

Glucose is a primary fuel for generating energy in basic daily activities. Thus, glucose homeostasis is tightly regulated by counter-regulatory hormones such as glucagon, cortisol, and insulin, which affect key organs including liver, skeletal muscle, pancreas, and adipocytes. Among metabolic tissues, liver plays a critical role in controlling glucose production under various hormonal and metabolic cues. Under fasting, acute activation of both glycogenolysis and gluconeogenesis is achieved by post-translational modification or allosteric activation of key rate-limiting enzymes, thereby enabling enhanced glucose production from the liver to maintain glucose homeostasis. More prolonged fasting or starvation leads to the chronic activation of gluconeogenesis that requires increased expression of key enzymes in the pathway, which is turned off under feeding conditions by the molecular events that are initiated by insulin. This process is normally achieved by the regulation of gene expression at the level of transcription. Recently, the transcriptional regulators of hepatic gluconeogenesis are considered as potential therapeutic targets for the treatment of type 2 diabetes. In this review, we would like to discuss the current knowledge regarding the key transcriptional activators and inhibitors of hepatic gluconeogenic program to provide the better insight into the control of glycemia in the disease status.

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Acknowledgments

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Ministry of Education, Science and Technology, Korea (2011-0016454, 2011-0019448).

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  1. Division of Biochemistry and Molecular Biology, Department of Molecular Cell Biology and Samsung Biomedical Institute, Sungkyunkwan University School of Medicine, 300 Chunchun-dong, Jangan-gu, Suwon, 440-746, Gyeonggi-do, Korea

    Kyoung-Jin Oh, Hye-Sook Han, Min-Jung Kim & Seung-Hoi Koo

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Oh, KJ., Han, HS., Kim, MJ. et al. Transcriptional regulators of hepatic gluconeogenesis. Arch. Pharm. Res. 36, 189–200 (2013). https://doi.org/10.1007/s12272-013-0018-5

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