Metformin: An Old Drug for the Treatment of Diabetes but a New Drug for the Protection of the Endothelium.
Metformin: An Old Drug for the Treatment of Diabetes but a New Drug for the Protection of the Endothelium.
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DOI：
10.1159/000381643
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Triggle CR
中科院分区：
文献类型：
--
作者：
Kinaan M;Ding H;Triggle CR
抗糖尿病和口服降糖药二甲双胍于1958年首次用于临床，今天是治疗2型糖尿病和多囊卵巢疾病的首选或“金标准”药物。二甲双胍对糖尿病的治疗特别重要，它能预防糖尿病引起的血管疾病。此外，回顾性分析表明，二甲双胍治疗为几种癌症患者提供了治疗获益。尽管二甲双胍的临床应用已有近60年，但其确切的细胞作用模式仍存在争议。在许多研究中已经推断出腺苷一磷酸（AMP）激活的蛋白激酶（AMPK）（细胞的燃料计量器）的直接或间接作用，有证据表明AMPK的激活可能是由于二甲双胍对线粒体复合物1的轻度抑制作用，这反过来会提高AMP并激活AMPK。然而，体外研究中使用的二甲双胍浓度与治疗水平之间的差异表明，在将基于细胞的研究得出的推论扩展到患者中观察到的治疗获益之前，应谨慎行事。可以想象，这些效应或其中一些效应可能至少部分独立于AMPK和/或线粒体呼吸，并反映了二甲双胍或二甲双胍的次要且尚未鉴定的推定代谢产物对靶蛋白/信号级联的直接效应。在这篇综述中，我们对二甲双胍口服降血糖、胰岛素增敏和血管保护作用的药代动力学特性以及细胞和临床基础研究的数据进行了严格评估。
The anti-diabetic and oral hypoglycaemic agent metformin, first used clinically in 1958, is today the first choice or ‘gold standard’ drug for the treatment of type 2 diabetes and polycystic ovary disease. Of particular importance for the treatment of diabetes, metformin affords protection against diabetes-induced vascular disease. In addition, retrospective analyses suggest that treatment with metformin provides therapeutic benefits to patients with several forms of cancer. Despite almost 60 years of clinical use, the precise cellular mode(s) of action of metformin remains controversial. A direct or indirect role of adenosine monophosphate (AMP)-activated protein kinase (AMPK), the fuel gauge of the cell, has been inferred in many studies, with evidence that activation of AMPK may result from a mild inhibitory effect of metformin on mitochondrial complex 1, which in turn would raise AMP and activate AMPK. Discrepancies, however, between the concentrations of metformin used in in vitro studies versus therapeutic levels suggest that caution should be applied before extending inferences derived from cell-based studies to therapeutic benefits seen in patients. Conceivably, the effects, or some of them, may be at least partially independent of AMPK and/or mitochondrial respiration and reflect a direct effect of either metformin or a minor and, as yet, unidentified putative metabolite of metformin on a target protein(s)/signalling cascade. In this review, we critically evaluate the data from studies that have investigated the pharmacokinetic properties and the cellular and clinical basis for the oral hypoglycaemic, insulin-sensitising and vascular protective effects of metformin.
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影响因子：
4
作者：
Caton, Paul W.;Nayuni, Nanda K.;Corder, Roger
通讯作者：
Corder, Roger
影响因子：
7.3
作者：
Arunachalam G;Samuel SM;Marei I;Ding H;Triggle CR
通讯作者：
Triggle CR
影响因子：
4.7
作者：
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Albini A
影响因子：
64.8
作者：
Cunningham, John T.;Rodgers, Joseph T.;Puigserver, Pere
通讯作者：
Puigserver, Pere
影响因子：
5.1
作者：
Bener, Abdulbari;Zirie, Mahmoud;Wareham, Nick J.
通讯作者：
Wareham, Nick J.