New Insight into the Effects of Metformin on Diabetic Retinopathy, Aging and Cancer: Nonapoptotic Cell Death, Immunosuppression, and Effects beyond the AMPK Pathway.
Sheng-Kai Hsu,Kai-Chun Cheng,Miracle Oluebube Mgbeahuruike,Yi-Hsiung Lin,Chang-Yi Wu,Chang-Yi Wu,Hui-Min David Wang,Chia-Hung Yen,Chien-Chih Chiu,Shwu-Jiuan Sheu +9 more
Reads0
Chats0
TLDR
In this article, the anticancer effects of metformin and its potential modulation of several novel types of non-apoptotic cell death, including ferroptosis, pyroptoses, and necroptosis are discussed.Abstract:
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.read more
Citations
More filters
Journal ArticleDOI
A Clinical Perspective of the Multifaceted Mechanism of Metformin in Diabetes, Infections, Cognitive Dysfunction, and Cancer
TL;DR: Both clinical and mechanistic studies support the pluripotent effects of metformin on reducing cardiovascular–renal events, infection, cancer, cognitive dysfunction, and all-cause death in type 2 diabetes, making this low-cost medication a fundamental therapy for individualization of other glucose-lowering drugs in type 1 diabetes.
Journal ArticleDOI
Metformin Protects against Spinal Cord Injury and Cell Pyroptosis via AMPK/NLRP3 Inflammasome Pathway
TL;DR: This study confirmed that MET inhibits neuronal pyroptosis after SCI via the AMPK/NLRP3 signaling pathway, which is mostly dependent on the AM PK pathway increase, hence decreasing NLRP3 inflammasome activation.
Journal ArticleDOI
Diabetic retinopathy as the leading cause of blindness and early predictor of cascading complications—risks and mitigation
Martina Kropp,Olga Golubnitschaja,Alena Mazurakova,Lenka Koklesova,Nafiseh Sargheini,Trong-Tin Kevin Steve Vo,Eline De Clerck,Jiri Polivka,Pavel Potužník,Ivana Stetkarova,Peter Kubatka,Gabriele Thumann +11 more
TL;DR: In this article , the authors proposed a predictive approach to develop diagnosis and treatment algorithms tailored to the individual for a cost-effective early prevention by implementing the paradigm shift from reactive medicine to predictive, preventive, and personalized medicine (PPPM) in primary and secondary diabetic care management.
Journal ArticleDOI
Iron metabolism and ferroptosis in type 2 diabetes mellitus and complications: mechanisms and therapeutic opportunities
TL;DR: In this article , the authors summarized the connection between the metabolic pathways and molecular mechanisms of iron metabolism and ferroptosis in Type 2 diabetes mellitus (T2DM) and discussed the potential targets and pathways concerning ferroidosis in treating T2DM.
Journal ArticleDOI
Metformin Improves the Senescence of Renal Tubular Epithelial Cells in a High-Glucose State Through E2F1
Dan Liang,Zhiyang Li,Zhao Chun Feng,Zhiping Yuan,Yunling Dai,Xin Wu,Fan Zhang,Yuanyuan Wang,Yuxia Zhou,Lingling Liu,Mingjun Shi,Ying Xiao,Bing Guo +12 more
TL;DR: It is shown that metformin alleviates high-glucose-induced senescence and fibrosis of renal tubular epithelial cells by downregulating the expression of E2F1.
References
More filters
Journal ArticleDOI
Acquired Resistance of Lung Adenocarcinomas to Gefitinib or Erlotinib Is Associated with a Second Mutation in the EGFR Kinase Domain
William Pao,Vincent A. Miller,Katerina Politi,Gregory J. Riely,Romel Somwar,Maureen F. Zakowski,Mark G. Kris,Harold E. Varmus +7 more
TL;DR: Biochemical analyses of transfected cells and growth inhibition studies with lung cancer cell lines demonstrate that the T790M mutation confers resistance to EGFR mutants usually sensitive to either gefitinib or erlotinib, which should help guide the search for more effective therapy against a specific subset of lung cancers.
Journal ArticleDOI
The AMPK signalling pathway coordinates cell growth, autophagy and metabolism
TL;DR: A number of recent breakthroughs in the mechanistic understanding of AMPK function are reviewed, focusing on a number of newly identified downstream effectors of AM PK.
Journal ArticleDOI
Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase
Hideki Shimura,Nobutaka Hattori,Shin-ichiro Kubo,Yoshikuni Mizuno,Shuichi Asakawa,Shinsei Minoshima,Nobuyoshi Shimizu,Kazuhiro Iwai,Tomoki Chiba,Keiji Tanaka,Toshiaki Suzuki +10 more
TL;DR: The findings indicate that accumulation of proteins that have yet to be identified causes a selective neural cell death without formation of Lewy bodies, and should enhance the exploration of the molecular mechanisms of neurodegeneration in Parkinson disease as well as in other Neurodegenerative diseases that are characterized by involvement of abnormal protein ubiquitination.
Journal ArticleDOI
Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards
Vincenzo Bronte,Sven Brandau,Shu Hsia Chen,Mario P. Colombo,Alan B. Frey,Tim F. Greten,Susanna Mandruzzato,Peter J. Murray,Augusto C. Ochoa,Suzanne Ostrand-Rosenberg,Paulo C. Rodriguez,Antonio Sica,Viktor Umansky,Viktor Umansky,Robert H. Vonderheide,Dmitry I. Gabrilovich +15 more
TL;DR: The authors identify the challenges and proposed set of minimal reporting guidelines for mouse and human MDSC are a heterogeneous population expanded in cancer and other chronic inflammatory conditions.
Journal ArticleDOI
Pore-forming activity and structural autoinhibition of the gasdermin family
Jingjin Ding,Kun Wang,Wang Liu,Yang She,Qi Sun,Jianjin Shi,Hanzi Sun,Da-Cheng Wang,Da-Cheng Wang,Feng Shao +9 more
TL;DR: It is demonstrated that the liposome-leakage and pore-forming activities of the gasdermin-N domain are required for pyroptosis and provide insights into the roles of theGasdermin family in necrosis, immunity and diseases.