Metformin and metabolic diseases: a focus on hepatic aspects.
Metformin and metabolic diseases: a focus on hepatic aspects.
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DOI：
10.1007/s11684-015-0384-0
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发表时间：
2015-06
影响因子：
8.1
通讯作者：
Wu C
中科院分区：
文献类型：
--
作者：
Zheng J;Woo SL;Hu X;Botchlett R;Chen L;Huo Y;Wu C
二甲双胍已被广泛用作治疗2型糖尿病（T2D）的一线抗糖尿病药物。作为一种主要靶向肝脏的药物，二甲双胍抑制肝葡萄糖生成（HGP），这是二甲双胍改善T2D高血糖症的主要机制。在生物化学上，二甲双胍抑制糖原合成并刺激糖酵解。二甲双胍还抑制糖原分解，这是一种对HGP升高起关键作用的途径。二甲双胍在对高血糖产生有益作用的同时，还可改善胰岛素抵抗并纠正T2D患者的血脂异常。二甲双胍的这些有益作用暗示了二甲双胍在管理非酒精性脂肪性肝病中的作用。正如人类和动物研究结果所支持的，二甲双胍可改善肝脏脂肪变性并抑制肝脏炎症。二甲双胍对肝脏方面的有益作用在机制上通过腺苷一磷酸活化蛋白激酶（AMPK）依赖性和AMPK非依赖性途径介导。此外，二甲双胍通常是安全的，也可能使其他慢性肝病患者受益。
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.