二甲双胍作用新机制

Novel action mechanism of metformin

二甲双胍是全世界多个指南推荐的在没有禁忌时2型糖尿病的一线降糖用药,其作用机制一直备受关注,然而至今仍未完全明确。经典理论认为二甲双胍可直接作用于肝细胞,通过活化AMPK等机制来发挥其降糖功效。近期,研究发现二甲双胍可调节肠道菌群,减少肠道菌群中的脆弱拟杆菌,使特定胆汁酸升高,进而以不依赖AMPK的方式抑制肠道FXR信号,从而达到降糖作用;一些研究还发现二甲双胍通过抑制果糖1,6-二磷酸酶-1的活性,从而降低肝脏葡萄糖生成。还有不同的研究发现二甲双胍具有调节肠道菌群从而延缓衰老的功效,并有研究发现二甲双胍在抗癌方面也有着很好的作用。本文就近几年对二甲双胍新的作用机制研究结果进行综述。

Metformin is the first-line antidiabetic drugs for type 2 diabetes if it is not contraindicated and tolerated,and its action mechanism has been paid much attention to, however, the controversies about it still exist.The classic theory considers that metformin acts directly on hepatocytes to produce hypoglycemic effects through activating protein kinase (AMPK) activity.Recently, the researches have found that metformin can modulate intestinal tract flora, decrease Bacteroides fragilis in intestinal tract flora to increase specific bile acid to inhibit intestinal FXR signaling in an AMPK-independent manner,so as to lower blood glucose.Some researches have found that metformin can decrease the glucogenesis in liver by inhibiting the activity of fructose-1-6-bisphosphatase,moreover,the other researches have found that metformin has the effects of delaying senility by regulating intestinal tract flora,and metformin has better anticancer effects.This article will review the new action mechanism of metformin in the research results in recent years.