二甲双胍
医学
肾
药理学
糖尿病
机制(生物学)
内科学
重症监护医学
内分泌学
物理
量子力学
作者
Anni Song,Chun Zhang,Xianfang Meng
标识
DOI:10.1016/j.biopha.2021.111454
摘要
Metformin is an oral antihyperglycemic drug widely used to treat type 2 diabetes mellitus (T2DM), acting via indirect activation of 5′ Adenosine monophosphate-activated Protein Kinase (AMPK). Beyond the anti-diabetic effect, accumulative pieces of evidence have revealed that metformin also everts a beneficial effect in diverse kidney diseases. In various acute kidney diseases (AKI) animal models, metformin protects renal tubular cells from inflammation, apoptosis, reactive oxygen stress (ROS), endoplasmic reticulum (ER) stress, epithelial-mesenchymal transition (EMT) via AMPK activation. In diabetic kidney disease (DKD), metformin also alleviates podocyte loss, mesangial cells apoptosis, and tubular cells senescence through AMPK-mediated signaling pathways. Besides, metformin inhibits cystic fibrosis transmembrane conductance regulator (CFTR)-mediated fluids secretion and the mammalian target of rapamycin (mTOR)-involved cyst formation negatively regulated by AMPK in autosomal dominant polycystic kidney disease (APDKD). Furthermore, metformin also contributes to the alleviation of urolithiasis and renal cell carcinoma (RCC). As the common pathway for chronic kidney disease (CKD) progressing towards end-stage renal disease (ESRD), renal fibrosis is ameliorated by metformin, to a great extent dependent on AMPK activation. However, clinical data are not always consistent with preclinical data, some clinical investigations showed the unmeaningful even detrimental effect of metformin on T2DM patients with kidney diseases. Most importantly, metformin-associated lactic acidosis (MALA) is a vital issue restricting the application of metformin. Thus, we conclude the application of metformin in kidney diseases and uncover the underlying molecular mechanisms in this review. • Beyond the anti-diabetic effect, metformin also everts the pleiotropic effects in diverse renal diseases. • Metformin plays a renoprotective role in various kidney diseases under different etiologic settings. • Metformin should be carefully administered to patients with impaired renal function.
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