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Front. Endocrinol. | doi: 10.3389/fendo.2018.00802

Unraveling the regulation of hepatic gluconeogenesis

  • 1West China Hospital, Sichuan University, China

Hepatic gluconeogenesis, de novo glucose synthesis from available precursors, plays a crucial role in maintaining glucose homeostasis to meet energy demands during the prolonged starvation in animals. The abnormally increased rate of hepatic gluconeogenesis contributes to the hyperglycemia of diabetes. Gluconeogenesis is regulated on multiple levels, such as hormonal secretion, gene transcription and posttranslational modification. We review here the molecular mechanisms underlying the transcriptional regulation of gluconeogenesis in response to nutritional and hormonal changes. The nutrient state determines the hormone release, which instigates the signaling cascades in the liver to modulate the activities of various transcriptional factors through various post-translational modifications phosphorylation, methylation and acetylation. AMP-activated protein kinase (AMPK) can mediate the activities of some transcription factors, however its role in the regulation of gluconeogenesis remains uncertain. Metformin, a primary hypoglycemic agent of type 2 diabetes, ameliorates hyperglycemia predominantly through suppression of hepatic gluconeogenesis. Several molecular mechanisms have been proposed to be metformin’s mode of action.

Keywords: Hepatic gluconeogenesis, hormone, Transcriptional (regulation), AMPK 5' AMP-activated protein kinase, postranslational modifications, Diabete mellitus, Methylation, Acetylation & phosphorylation, Metformin

Received: 18 Oct 2018; Accepted: 20 Dec 2018.

Edited by:

Åke Sjöholm, Division of Endocrinology and Diabetology, Department of Internal Medicine, Gävle Hospital, Sweden

Reviewed by:

Juei-Tang Cheng, Chang Jung Christian University, Taiwan
Yan Lu, Zhongshan Hospital, Fudan University, China
Benoit Viollet, Institut National de la Santé et de la Recherche Médicale (INSERM), France  

Copyright: © 2018 Xueping, Jinglu, Shanshan and Su. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Zhiguang Su, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China, zhiguang.su@scu.edu.cn