Szymczak-Pajor Izabela, Wenclewska Sylwia, Śliwińska Agnieszka
Department of Nucleic Acid Biochemistry, Medical University of Lodz, 251 Pomorska Str., 92-213 Lodz, Poland.
Department of Internal Medicine, Diabetology and Clinical Pharmacology, Medical University of Lodz, 251 Pomorska Str., 92-213 Lodz, Poland.
Pharmaceuticals (Basel). 2022 Jun 30;15(7):810. doi: 10.3390/ph15070810.
Metformin, a cheap and safe biguanide derivative, due to its ability to influence metabolism, is widely used as a first-line drug for type 2 diabetes (T2DM) treatment. Therefore, the aim of this review was to present the updated biochemical and molecular effects exerted by the drug. It has been well explored that metformin suppresses hepatic glucose production in both AMPK-independent and AMPK-dependent manners. Substantial scientific evidence also revealed that its action is related to decreased secretion of lipids from intestinal epithelial cells, as well as strengthened oxidation of fatty acids in adipose tissue and muscles. It was recognized that metformin's supra-therapeutic doses suppress mitochondrial respiration in intestinal epithelial cells, whereas its therapeutic doses elevate cellular respiration in the liver. The drug is also suggested to improve systemic insulin sensitivity as a result of alteration in gut microbiota composition, maintenance of intestinal barrier integrity, and alleviation of low-grade inflammation.
二甲双胍是一种廉价且安全的双胍衍生物，因其能够影响新陈代谢，被广泛用作治疗2型糖尿病（T2DM）的一线药物。因此，本综述的目的是介绍该药物最新的生化和分子作用。已有充分研究表明，二甲双胍以不依赖AMPK和依赖AMPK的方式抑制肝脏葡萄糖生成。大量科学证据还表明，其作用与肠道上皮细胞脂质分泌减少以及脂肪组织和肌肉中脂肪酸氧化增强有关。人们认识到，二甲双胍的超治疗剂量会抑制肠道上皮细胞的线粒体呼吸，而其治疗剂量会提高肝脏中的细胞呼吸。该药物还被认为可通过改变肠道微生物群组成、维持肠道屏障完整性以及减轻低度炎症来改善全身胰岛素敏感性。
