摘要
背景:糖尿病肾病是糖尿病患者最重要的并发症之一。对于糖尿病肾病的发病机制至关重要的主要步骤包括通过AMP激活激酶(AMPK)和哺乳动物雷帕霉素(mTOR),活性氧产生和糖尿病或高血糖条件下的内质网应激调节细胞信号传导。这些过程介导肾细胞的增加的损失,例如足细胞,其相应地导致肾损伤和肾功能的丧失,例如糖尿病肾病中的结构完整性和肾小球滤过。抗糖尿病药二甲双胍广泛用于糖尿病患者的药物治疗。除了抗糖尿病作用外,最近的研究发现二甲双胍在体外和体内都有额外的肾保护作用。发现二甲双胍在不同的实验肾脏环境中减少凋亡。此外,显示出可以减少糖尿病大鼠以及2型糖尿病患者的白蛋白尿。证明这些作用是通过AMPK / mTOR信号轴介导的。这些数据表明二甲双胍对糖尿病肾病的有益和肾脏保护作用。目的:在本次综述中,我们将总结二甲双胍体外和体内肾保护作用的最新发现。此外,我们将描述和讨论这种药物治疗糖尿病肾病的治疗潜力。
关键词: 二甲双胍,高血糖,糖尿病肾病,肾脏,肾损伤,糖尿病,足细胞,AMP激活蛋白激酶。
Current Medicinal Chemistry
Title:Update on the Protective Renal Effects of Metformin in Diabetic Nephropathy
Volume: 24 Issue: 31
关键词: 二甲双胍,高血糖,糖尿病肾病,肾脏,肾损伤,糖尿病,足细胞,AMP激活蛋白激酶。
摘要: Background: Diabetic nephropathy is one of the most important complications in patients with diabetes mellitus. Main steps crucial for the pathogenesis of diabetic nephropathy involve amongst others the modulation of cell signaling via AMP-activated kinase (AMPK) and mammalian target of rapamycin (mTOR), reactive oxygen generation, and endoplasmic reticulum stress under diabetic or hyperglycemic conditions. These processes mediate increased loss of renal cells, such as podocytes, which consequentially leads to renal damage and loss of renal functions, such as structural integrity and glomerular filtration in diabetic nephropathy. The anti-diabetic drug metformin has been widely used for pharmacotherapeutic treatment of patients with diabetes mellitus. Besides its anti-diabetic actions, recent studies revealed additional nephroprotective effects of metformin in vitro and in vivo. Metformin was found to diminish apoptosis in different experimental renal settings. Moreover, it was shown to reduce albuminuria in diabetic rats as well as in patients with type 2 diabetes mellitus. These effects were demonstrated to be mediated via the AMPK/mTOR signaling axis. These data indicate beneficial and renoprotective effects of metformin in diabetic nephropathy.
Objective: In this review, we will summarize the latest findings regarding the nephroprotective impact of metformin in vitro and in vivo. Moreover, we will depict and discuss the therapeutic potential of this drug for the treatment of diabetic nephropathy.
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Cite this article as:
Update on the Protective Renal Effects of Metformin in Diabetic Nephropathy, Current Medicinal Chemistry 2017; 24 (31) . https://dx.doi.org/10.2174/0929867324666170404143102
DOI https://dx.doi.org/10.2174/0929867324666170404143102 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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