Santomauro Júnior Augusto Cézar, Ugolini Michelle Remião, Santomauro Ana Teresa, Souto Ricardo Peres do
Faculdade de Medicina do ABC, Santo André, SP, Brazil.
Arq Bras Endocrinol Metabol. 2008 Feb;52(1):120-5. doi: 10.1590/s0004-27302008000100017.
Metformin is one of the most commonly prescribed oral antidiabetic agents worldwide. However, its mechanism of action remains unknown. The Diabetes Prevention Program Research Group studies have shown that metformin administration and lifestyle-intervention (diet and exercise) reduce the incidence of Diabetes Mellitus type 2 (DM2). A possible biochemical connection between both therapies may be the AMP-activated protein kinase (AMPK). This enzyme was originally described as a sensor of cellular energy status, being activated in exercise. On the other hand, several experimental evidences indicate that AMPK may be an important target of metformin action. This paper discusses various ways for AMPK regulation, suggesting a possible mechanism for its activation by metformin that involves the production of reactive nitrogen species. AMPK activation determines a wide variety of physiological effects, including enhanced glucose uptake by skeletal muscle and enhanced lipid catabolism. Thus, it may be a key player not only in the prevention and treatment of DM2, but also in the development of new treatments for obesity and the metabolic syndrome. The finding of AMPK activation by metformin draws attention to this enzyme as an important pharmacological target.
二甲双胍是全球最常用的口服抗糖尿病药物之一。然而，其作用机制尚不清楚。糖尿病预防计划研究小组的研究表明，服用二甲双胍和进行生活方式干预（饮食和运动）可降低2型糖尿病（DM2）的发病率。两种治疗方法之间可能的生化联系可能是AMP激活的蛋白激酶（AMPK）。这种酶最初被描述为细胞能量状态的传感器，在运动中被激活。另一方面，一些实验证据表明，AMPK可能是二甲双胍作用的重要靶点。本文讨论了AMPK调节的各种方式，提出了二甲双胍激活AMPK的一种可能机制，该机制涉及活性氮物质的产生。AMPK激活决定了多种生理效应，包括增强骨骼肌对葡萄糖的摄取和增强脂质分解代谢。因此，它可能不仅是预防和治疗DM2的关键因素，也是开发肥胖症和代谢综合征新疗法的关键因素。二甲双胍激活AMPK这一发现使人们将注意力投向这种酶，将其作为一个重要的药理学靶点。
