New Insight into the Effects of Metformin on Diabetic Retinopathy, Aging and Cancer: Nonapoptotic Cell Death, Immunosuppression, and Effects beyond the AMPK Pathway.
New Insight into the Effects of Metformin on Diabetic Retinopathy, Aging and Cancer: Nonapoptotic Cell Death, Immunosuppression, and Effects beyond the AMPK Pathway.
复制标题
DOI：
10.3390/ijms22179453
复制
发表时间：
2021-08-31
影响因子：
5.6
通讯作者：
Sheu SJ
中科院分区：
文献类型：
--
作者：
Hsu SK;Cheng KC;Mgbeahuruike MO;Lin YH;Wu CY;Wang HD;Yen CH;Chiu CC;Sheu SJ
在代谢应激条件下，例如缺氧和葡萄糖剥夺，AMP：ATP比率的增加激活AMP活化蛋白激酶（AMPK）途径，导致细胞代谢的调节。广泛用于2型糖尿病（T2DM）患者的二甲双胍通过抑制肝脏血管生成和促进胰岛素敏感性以促进细胞对葡萄糖的摄取来调节血糖。在分子水平上，二甲双胍介导的细胞保护的最熟知的机制是AMPK通路激活，其调节代谢并保护细胞免于降解或致病性变化，例如与衰老和糖尿病视网膜病变（DR）相关的那些。最近，它已被发现，二甲双胍的行为通过AMPK和非AMPK介导的途径，发挥超出糖尿病治疗，可能会防止衰老和改善DR相关的影响。本次审查的重点是新的见解，二甲双胍的抗癌作用及其潜在的调制几种新型的非凋亡性细胞死亡，包括铁凋亡，pyroptosis和necroptosis。此外，还讨论了二甲双胍的抗转移和免疫抑制作用及其假设机制，突出了未来有希望的癌症预防策略。
Under metabolic stress conditions such as hypoxia and glucose deprivation, an increase in the AMP:ATP ratio activates the AMP-activated protein kinase (AMPK) pathway, resulting in the modulation of cellular metabolism. Metformin, which is widely prescribed for type 2 diabetes mellitus (T2DM) patients, regulates blood sugar by inhibiting hepatic gluconeogenesis and promoting insulin sensitivity to facilitate glucose uptake by cells. At the molecular level, the most well-known mechanism of metformin-mediated cytoprotection is AMPK pathway activation, which modulates metabolism and protects cells from degradation or pathogenic changes, such as those related to aging and diabetic retinopathy (DR). Recently, it has been revealed that metformin acts via AMPK- and non-AMPK-mediated pathways to exert effects beyond those related to diabetes treatment that might prevent aging and ameliorate DR. This review focuses on new insights into the anticancer effects of metformin and its potential modulation of several novel types of nonapoptotic cell death, including ferroptosis, pyroptosis, and necroptosis. In addition, the antimetastatic and immunosuppressive effects of metformin and its hypothesized mechanism are also discussed, highlighting promising cancer prevention strategies for the future.
登录
查看更多内容
影响因子：
4.6
作者：
Endo H;Owada S;Inagaki Y;Shida Y;Tatemichi M
通讯作者：
Tatemichi M
二甲双胍通过抑制肿瘤相关巨噬细胞的 M2 样极化来预防癌症转移
影响因子：
--
作者：
Ding L;Liang G;Yao Z;Zhang J;Liu R;Chen H;Zhou Y;Wu H;Yang B;He Q
通讯作者：
He Q
二甲双胍通过表观遗传机制通过 IDH1 诱导 Nrf2 表达使子宫内膜癌细胞对化疗敏感
影响因子：
8
作者：
Bai, Mingzhu;Yang, Linlin;Zheng, Wenxin
通讯作者：
Zheng, Wenxin
影响因子：
9
作者：
通讯作者：
--
影响因子：
64.8
作者：
Ding, Jingjin;Wang, Kun;Shao, Feng
通讯作者：
Shao, Feng