Molecular Mechanisms of Metformin for Diabetes and Cancer Treatment.

Molecular Mechanisms of Metformin for Diabetes and Cancer Treatment.
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DOI:
10.3389/fphys.2018.01039
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发表时间:
2018
影响因子:
4
通讯作者:
Lu Y
Lu Y
中科院分区:
医学2区
文献类型:
--
作者:
Li M;Li X;Zhang H;Lu Y

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二甲双胍作为治疗高血糖和胰岛素抵抗的一线药物已有50多年的历史。然而,其治疗作用的分子基础仍不完全清楚。最新进展表明,二甲双胍可通过多种机制发挥其降糖作用,包括激活5′-AMP活化蛋白激酶、减少环AMP的产生、抑制电子传递链的线粒体复合物I、靶向甘油磷酸脱氢酶以及改变肠道微生物组。此外,流行病学和临床观察研究表明,二甲双胍降低了2型糖尿病患者的癌症风险,并改善了人类癌症的生存结局。实验研究表明,该药物可以通过抑制mTORC 1信号和线粒体复合物I来抑制癌细胞的活力、生长和增殖,这表明它可能是一种有希望的恶性肿瘤候选药物。本文综述了二甲双胍在2型糖尿病和肿瘤发生中的最新研究进展,为人类疾病的治疗发展提供了新的视角。
Metformin has been the first-line drug treatment for hyperglycemia and insulin resistance for over 50 years. However, the molecular basis of its therapeutic role remained incompletely understood. Recent advances demonstrate that metformin could exert its glucose-lowering effect by multiple mechanisms, including activation of 5′-AMP-activated protein kinase, decreasing production of cyclic AMP, suppressing mitochondrial complex I of the electron transport chain, targeting glycerophosphate dehydrogenase, and altering the gut microbiome. In addition, epidemiological and clinical observation studies suggest that metformin reduced cancer risk in patients with type 2 diabetes and improved survival outcome of human cancers. Experimental studies have shown that this drug can inhibit cancer cell viability, growth, and proliferation through inhibiting mTORC1 signaling and mitochondrial complex I, suggesting that it may be a promising drug candidate for malignancy. Here, we summarize recent progress in studies of metformin in type 2 diabetes and tumorigenesis, which provides novel insight on the therapeutic development of human diseases.
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