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Frontiers of Medicine

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ISSN 2095-0225(Online)

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Front. Med.    2015, Vol. 9 Issue (2) : 173-186    https://doi.org/10.1007/s11684-015-0384-0
REVIEW
Metformin and metabolic diseases: a focus on hepatic aspects
Juan Zheng1,2,*(),Shih-Lung Woo1,Xiang Hu1,2,Rachel Botchlett1,Lulu Chen2,Yuqing Huo3,Chaodong Wu1,*()
1. Department of Nutrition and Food Science, Texas A&M University, College Station, TX 77843, USA
2. Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
3. Drug Discovery Center, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen 518055, China
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Abstract

Metformin has been widely used as a first-line anti-diabetic medicine for the treatment of type 2 diabetes (T2D). As a drug that primarily targets the liver, metformin suppresses hepatic glucose production (HGP), serving as the main mechanism by which metformin improves hyperglycemia of T2D. Biochemically, metformin suppresses gluconeogenesis and stimulates glycolysis. Metformin also inhibits glycogenolysis, which is a pathway that critically contributes to elevated HGP. While generating beneficial effects on hyperglycemia, metformin also improves insulin resistance and corrects dyslipidemia in patients with T2D. These beneficial effects of metformin implicate a role for metformin in managing non-alcoholic fatty liver disease. As supported by the results from both human and animal studies, metformin improves hepatic steatosis and suppresses liver inflammation. Mechanistically, the beneficial effects of metformin on hepatic aspects are mediated through both adenosine monophosphate-activated protein kinase (AMPK)-dependent and AMPK-independent pathways. In addition, metformin is generally safe and may also benefit patients with other chronic liver diseases.
Keywords metformin      diabetes      hepatic steatosis      inflammatory response      insulin resistance     
Corresponding Author(s): Juan Zheng,Chaodong Wu   
Just Accepted Date: 14 January 2015   Online First Date: 11 February 2015    Issue Date: 22 May 2015
 Cite this article:   
Juan Zheng,Shih-Lung Woo,Xiang Hu, et al. Metformin and metabolic diseases: a focus on hepatic aspects[J]. Front. Med., 2015, 9(2): 173-186.
 URL:  
https://academic.hep.com.cn/fmd/EN/10.1007/s11684-015-0384-0
https://academic.hep.com.cn/fmd/EN/Y2015/V9/I2/173
Fig.1  MOA: metformin for type 2 diabetes. Metformin targets hepatocytes and acts through both AMPK-dependent and AMPK-independent pathways to suppress hepatic glucose production (HGP), thereby improving hyperglycemia of type 2 diabetes. Metformin also inhibits hepatic lipogensis and stimulates liver fatty acid oxidation, thereby correcting dyslipidemia and improving insulin resistance. See text for details.
Fig.2  MOA: metformin for NAFLD. In hepatocytes, metformin suppresses lipogenesis and stimulates fatty acid oxidation, thereby decreasing hepatocyte production of palmitate. This improves hepatic steatosis and, in turn, decreases fat deposition-associated macrophage (Kupffer cell) proinflammatory activation. In both hepatocytes and macrophages, metformin inhibits inflammatory signaling to suppress the production of proinflammatory cytokines. This contributes to suppression of liver inflammation. See text for details.
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