Molecular mechanism of action of metformin: old or new insights?
Molecular mechanism of action of metformin: old or new insights?
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DOI：
10.1007/s00125-013-2991-0
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发表时间：
2013-09
期刊：
影响因子：
8.2
通讯作者：
Sakamoto, Kei
中科院分区：
文献类型：
--
作者：
Rena, Graham;Pearson, Ewan R.;Sakamoto, Kei
关键词：
2型糖尿病的治疗方法有哪些？在全球范围内，每年有超过1亿患者服用这种药物。二甲双胍是在靶向药物发现时代之前发现的，其分子作用机制仍然是糖尿病研究的一个活跃领域。我们对二甲双胍分子靶点的理解的提高可能使具有相似性质的第二代药物的靶向鉴定成为可能，这是迄今为止不可能的发展。5'AMP活化蛋白激酶（AMPK）介导二甲双胍抗高血糖作用的观点最近受到遗传功能丧失研究的挑战，十多年来首次将药物的AMPK非依赖性作用推到聚光灯下。该药物的关键AMPK非依赖性作用包括多年来已知的线粒体作用，并且仍然被认为是二甲双胍的主要作用部位。再加上最近关于AMPK对反调节激素胰高血糖素的非依赖性作用的证据，AMPK非依赖性药物作用的新范式正在开始形成。本文就二甲双胍的分子作用机制的研究进展作一综述。
Metformin is the first-line drug treatment for type 2 diabetes. Globally, over 100 million patients are prescribed this drug annually. Metformin was discovered before the era of target-based drug discovery and its molecular mechanism of action remains an area of vigorous diabetes research. An improvement in our understanding of metformin’s molecular targets is likely to enable target-based identification of second-generation drugs with similar properties, a development that has been impossible up to now. The notion that 5' AMP-activated protein kinase (AMPK) mediates the anti-hyperglycaemic action of metformin has recently been challenged by genetic loss-of-function studies, thrusting the AMPK-independent effects of the drug into the spotlight for the first time in more than a decade. Key AMPK-independent effects of the drug include the mitochondrial actions that have been known for many years and which are still thought to be the primary site of action of metformin. Coupled with recent evidence of AMPK-independent effects on the counter-regulatory hormone glucagon, new paradigms of AMPK-independent drug action are beginning to take shape. In this review we summarise the recent research developments on the molecular action of metformin.
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DOI：
10.1038/nrm3072
发表时间：
2011-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.8
作者：
El-Mir, MY;Nogueira, V;Leverve, X
通讯作者：
Leverve, X
DOI：
10.1900/rds.2011.8.369
发表时间：
2011-01-01
期刊：
The review of diabetic studies : RDS
影响因子：
--
作者：
Christensen, Mikkel;Bagger, Jonatan I;Knop, Filip K
通讯作者：
Knop, Filip K
影响因子：
5.8
作者：
Donnelly, L. A.;Morris, A. D.;Pearson, E. R.
通讯作者：
Pearson, E. R.
影响因子：
4
作者：
GAWLER, DJ;WILSON, A;HOUSLAY, MD
通讯作者：
HOUSLAY, MD