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Trends Endocrinol Metab. 2017 Dec;28(12):868-878. doi: 10.1016/j.tem.2017.10.007. Epub 2017 Nov 8.

Mitogen-Activated Protein Kinase Regulation in Hepatic Metabolism.

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Department of Pharmacology, Yale University, New Haven, CT 06520, USA. Electronic address:
Department of Pharmacology, Yale University, New Haven, CT 06520, USA; Program in Integrative Cell Signaling and Neurobiology of Metabolism, Yale University, New Haven, CT 06520, USA.


The mitogen-activated protein kinases (MAPKs) participate in a multitude of processes that control hepatic metabolism. The liver regulates glucose and lipid metabolism, and under pathophysiological conditions such as obesity, type 2 diabetes mellitus (T2DM), and non-alcoholic fatty liver disease (NAFLD) these processes become dysfunctional. Stress responses activate the hepatic MAPKs, and this is thought to impair insulin action and lipid metabolism. The MAPKs also activate the MAPK phosphatases (MKPs) which oppose their actions. How the MAPK/MKP balance is controlled in liver metabolism and how perturbations in these activities contribute to metabolic disease remains unclear. Discussion of recent insights into the MAPK/MKP signaling role in hepatic metabolic function and disease will be the focus of this review.


liver; metabolism; mitogen-activated protein kinase; obesity; signal transduction; type 2 diabetes

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