Kim Jeongho, You Young-Jai
Department of Biological Sciences, Inha University, Incheon, South Korea.
Nagoya Research Center for Brain and Neural Circuits, Graduate School of Science, Nagoya University, Nagoya, Japan.
IUBMB Life. 2017 Jul;69(7):459-469. doi: 10.1002/iub.1633. Epub 2017 Apr 26.
Metformin ameliorates hyperglycemia without the side effects of lactic acidosis or hypoglycemia. Metformin lowers the blood glucose level by decreasing hepatic glucose production in the liver and by increasing glucose uptake in the muscle. Recent studies show that metformin induces cell death in certain cancer cell lines by interfering with the metabolism of the cancer cells. Therefore, understanding the mechanisms of action for metformin will provide insights into how to better treat diabetes and other metabolic disorders and also into the development of new therapeutic drugs. One of the best understood molecular targets of metformin is the mitochondrial complex I. However, given metformin's broad effects on metabolism, it could act on multiple targets. In this review, we summarize current findings in metformin's mechanisms of action regarding its known targets in mitochondria and known effects in cancer cell lines. Then, we introduce endosomal Na /H exchangers and the V-ATPase as new potential targets of metformin's action. Finally, we will discuss the hypothesis that metformin directly acts on endosome/lysosome regulation so as to regulate metabolism and ultimately alleviate type 2 diabetes. © 2017 IUBMB Life, 69(7):459-469, 2017.
二甲双胍可改善高血糖，且无乳酸性酸中毒或低血糖等副作用。二甲双胍通过减少肝脏中肝糖生成以及增加肌肉对葡萄糖的摄取来降低血糖水平。最近的研究表明，二甲双胍通过干扰癌细胞的代谢在某些癌细胞系中诱导细胞死亡。因此，了解二甲双胍的作用机制将为更好地治疗糖尿病和其他代谢紊乱以及开发新的治疗药物提供思路。二甲双胍最广为人知的分子靶点之一是线粒体复合物I。然而，鉴于二甲双胍对代谢具有广泛影响，它可能作用于多个靶点。在本综述中，我们总结了目前关于二甲双胍作用机制的研究结果，涉及其在线粒体中的已知靶点以及在癌细胞系中的已知作用。然后，我们介绍内体钠/氢交换体和V-ATP酶作为二甲双胍作用的新潜在靶点。最后，我们将讨论二甲双胍直接作用于内体/溶酶体调节从而调节代谢并最终缓解2型糖尿病的假说。© 2017国际生物化学与分子生物学联盟生命科学，69(7):459 - 469，2017。
