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Metformin AND AMPK

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https://www.readbyqxmd.com/read/29684379/effect-of-a-long-term-treatment-with-metformin-in-dystrophic-mdx-mice-a-reconsideration-of-its-potential-clinical-interest-in-duchenne-muscular-dystrophy
#1
Paola Mantuano, Francesca Sanarica, Elena Conte, Maria Grazia Morgese, Roberta Francesca Capogrosso, Anna Cozzoli, Adriano Fonzino, Angelo Quaranta, Jean-Francois Rolland, Michela De Bellis, Giulia Maria Camerino, Luigia Trabace, Annamaria De Luca
The pharmacological stimulation of AMP-activated protein kinase (AMPK) via metabolic enhancers has been proposed as potential therapeutic strategy for Duchenne muscular dystrophy (DMD). Metformin, a widely-prescribed anti-hyperglycemic drug which activates AMPK via mitochondrial respiratory chain, has been recently tested in DMD patients in synergy with nitric oxide (NO)-precursors, with encouraging results. However, preclinical data supporting the use of metformin in DMD are still poor, and its actions on skeletal muscle appear controversial...
April 20, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29681936/metformin-regulating-mir-34a-pathway-to-inhibit-egr1-in-rat-mesangial-cells-cultured-with-high-glucose
#2
Can Wu, Ningning Qin, Huiwen Ren, Min Yang, Shuang Liu, Qiuyue Wang
Background: Activating AMPK α negatively regulates Egr1 to inhibit inflammatory cytokines in high glucose. miR-34a inhibition increases phosphorylated AMPK α through mediating SIRT1 to suppress the development of fatty liver. Aim of the Study: To clarify the function of Egr1 on the inflammation and fibrosis in high glucose-cultured MCs, as well as to explore the effects of metformin on miR-34a pathway and Egr1 expression. Methods: We transfected MCs with miR-34a inhibitor...
2018: International Journal of Endocrinology
https://www.readbyqxmd.com/read/29670844/the-eeffect-of-metformin-combined-with-calcium-vitamin-d-3-against-diet-induced-nonalcoholic-fatty-liver-disease
#3
Sara Shojaei Zarghani, Samin Abbaszadeh, Mohammad Alizadeh, Maryam Rameshrad, Alireza Garjani, Hamid Soraya
Purpose: Metformin is one of the most popular drugs tested against nonalcoholic fatty liver disease (NAFLD). The present study aimed to investigate whether calcium-vitamin D3 cosupplementation will intensify the effect of metformin on the prevention of high-fat, high-fructose (HFFr) diet-induced hepatic steatosis. Methods: Male wistar rats (210±16 g) were assigned into the following seven groups: a Control group to receive a standard chow and six HFFr-fed groups to receive diets containing either normal (0...
March 2018: Advanced Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29665787/valproic-acid-sensitizes-metformin-resistant-human-renal-cell-carcinoma-cells-by-upregulating-h3-acetylation-and-emt-reversal
#4
Muyun Wei, Shaowei Mao, Guoliang Lu, Liang Li, Xiaopeng Lan, Zhongxian Huang, Yougen Chen, Miaoqing Zhao, Yueran Zhao, Qinghua Xia
BACKGROUND: Metformin (Met) is a widely available diabetic drug and shows suppressed effects on renal cell carcinoma (RCC) metabolism and proliferation. Laboratory studies in RCC suggested that metformin has remarkable antitumor activities and seems to be a potential antitumor drug. But the facts that metformin may be not effective in reducing the risk of RCC in cancer clinical trials made it difficult to determine the benefits of metformin in RCC prevention and treatment. The mechanisms underlying the different conclusions between laboratory experiments and clinical analysis remains unclear...
April 17, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29663879/anti-cancer-effects-of-metformin-recent-evidences-for-its-role-in-prevention-and-treatment-of-cancer
#5
Masoumeh Kheirandish, Hamidreza Mahboobi, Maryam Yazdanparast, Warda Kamal, Mohammad A Kamal
Metformin is widely used for the management of type 2 diabetes mellitus (T2DM). Recently growing evidence has shown its anti-cancer effects. The results are mainly obtained from observational studies and thus, little information is available concerning the mechanisms of action. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) plays an important role in the mechanism of action of metformin. The anti-cancer mechanisms of metformin include direct and indirect effects. The direct effects of metformin include AMPK-independent and AMPK-dependent effects, whereas the decrease in glucose level, hyperinsulinemia, and Insulin-like growth factor 1 (IGF-1) level was considered its indirect effects...
April 16, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29662316/metformin-inhibits-proliferation-and-cytotoxicity-and-induces-apoptosis-via-ampk-pathway-in-cd19-chimeric-antigen-receptor-modified-t-cells
#6
Qian Mu, Miao Jiang, Yuzhu Zhang, Fei Wu, Hui Li, Wen Zhang, Fang Wang, Jiang Liu, Liang Li, Dongshan Wang, Wenjuan Wang, Shiwu Li, Haibo Song, Dongqi Tang
Background: CD19-chimericantigen receptor (CAR) modified T cells (CD19-CAR T cells) have been well documented to possess potent anti-tumor properties against CD19-expressingleukemia cells. As a traditional medicine, metformin has been widely used to treat type II diabetes mellitus and more recently has become a candidate for the treatment of cancer. However, no report has revealed the direct effect of metformin on CD19-CAR T cell biological function and its underling mechanisms. Purpose: The purpose of this research was to explore the effect of metformin on CD19-CAR T cell biological function and the mechanisms involved...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29659176/nrf2-attenuates-inflammatory-response-in-copd-emphysema-crosstalk-with-wnt3a-%C3%AE-catenin-and-ampk-pathways
#7
Wenhui Cui, Zhihui Zhang, Panpan Zhang, Jiao Qu, Cheng Zheng, Xiaoting Mo, Wencheng Zhou, Liang Xu, Hongwei Yao, Jian Gao
Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation and abnormal inflammatory response. Wnt/β-catenin and AMP-activated protein kinase (AMPK) have been shown to modulate lung inflammatory responses and injury. However, it remains elusive whether Wnt/β-catenin and AMPK modulate nuclear factor erythroid-2 related factor-2 (Nrf2)-mediated protective responses during the development of emphysema. Here we showed that treatment with a Wnt pathway activator (LiCl) reduced elastase-induced airspace enlargement and cigarette smoke extract (CSE)-induced lung inflammatory responses in WT mice, which was associated with increased activation of Nrf2 pathway...
April 16, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29656591/amp-activated-protein-kinase-dependent-induction-of-autophagy-by-erythropoietin-protects-against-spinal-cord-injury-in-rats
#8
Peng Wang, Zhong-Dong Xie, Chang-Nan Xie, Chao-Wei Lin, Ji-Li Wang, Li-Na Xuan, Chun-Wu Zhang, Yu Wang, Zhi-Hui Huang, Hong-Lin Teng
AIMS: Autophagy has been regarded as a promising therapeutic target for spinal cord injury (SCI). Erythropoietin (EPO) has been demonstrated to exhibit neuroprotective effects in the central nervous system (CNS); however, the molecular mechanisms of its protection against SCI remain unknown. This study aims to investigate whether the neuroprotective effects of EPO on SCI are mediated by autophagy via AMP-activated protein kinase (AMPK) signaling pathways. METHODS: Functional assessment and Nissl staining were used to investigate the effects of EPO on SCI...
April 15, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29620187/metformin-inhibits-ovarian-cancer-via-decreasing-h3k27-trimethylation
#9
Guiju Tang, Jianfeng Guo, Yapei Zhu, Zaiju Huang, Ting Liu, Jing Cai, Lili Yu, Zehua Wang
Metformin has been used for the treatment of type II diabetes mellitus for decades. Recently, used of metformin in the therapy of diverse human cancer types has received widespread attention, while the underlying mechanisms have been not fully elucidated. In the current study, 5-ethynyl-20-deoxyuridine assay to detect cell proliferation, flow cytometry to detect apoptosis, scratch wound healing and Transwell migration assay to detect cell migration capacity. The current study reported that metformin inhibited cell proliferation and migration, and promoted apoptosis in ovarian cancer cells, particularly under normoglycemic conditions in vitro...
March 29, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29618839/metformin-adapts-its-cellular-effects-to-bioenergetic-status-in-a-model-of-metabolic-dysfunction
#10
Christopher Auger, Thibacg Sivayoganathan, Abdikarim Abdullahi, Alexandra Parousis, Bo Wen Pang, Marc G Jeschke
Thermal injury induces a complex immunometabolic response, characterized by hyperglycemia, extensive inflammation and persistent hypermetabolism. It has been suggested that attenuation of the hypermetabolic response is beneficial for patient wellbeing. To that effect, metformin represents an attractive therapeutic agent, as its effects on glycemia, inflammation and bioenergetics can improve outcomes in burn patients. Therefore, we studied metformin and its effects on mitochondrial bioenergetics in a murine model of thermal injury...
April 4, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29614701/targeting-ampk-signaling-as-a-neuroprotective-strategy-in-parkinson-s-disease
#11
Daniel W Curry, Bernardo Stutz, Zane B Andrews, John D Elsworth
Parkinson's disease (PD) is the second most common neurodegenerative disorder. It is characterized by the accumulation of intracellular α-synuclein aggregates and the degeneration of nigrostriatal dopaminergic neurons. While no treatment strategy has been proven to slow or halt the progression of the disease, there is mounting evidence from preclinical PD models that activation of 5'-AMP-activated protein kinase (AMPK) may have broad neuroprotective effects. Numerous dietary supplements and pharmaceuticals (e...
March 26, 2018: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/29610348/activation-of-ampk-by-metformin-improves-withdrawal-signs-precipitated-by-nicotine-withdrawal
#12
Julia K Brynildsen, Bridgin G Lee, Isaac J Perron, Sunghee Jin, Sangwon F Kim, Julie A Blendy
Cigarette smoking is the leading cause of preventable disease and death in the United States, with more persons dying from nicotine addiction than any other preventable cause of death. Even though smoking cessation incurs multiple health benefits, the abstinence rate remains low with current medications. Here we show that the AMP-activated protein kinase (AMPK) pathway in the hippocampus is activated following chronic nicotine use, an effect that is rapidly reversed by nicotine withdrawal. Increasing pAMPK levels and, consequently, downstream AMPK signaling pharmacologically attenuate anxiety-like behavior following nicotine withdrawal...
April 2, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29593575/dai-zong-fang-a-traditional-chinese-herbal-formula-ameliorates-insulin-resistance-in-db-db-mice
#13
Lili Zhu, Xiaoyun Zhu, Guibo Sun, Xiangbao Meng, Min Wang, Hanming Cui, Jialong Wang, Yadong Zhai, Ke Yang, Yang Tang, Xiaobo Sun, Ximing Liu
Intricate health problems, such as insulin resistance (IR) and its associated diseases, call for multi-targeted therapies with few side effects. Based on traditional Chinese medicine (TCM), Dai-Zong-Fang (DZF) is an herbal formula mainly composed of Rhizoma Coptidis (Huanglian) and Fructus Aurantii Immaturus (Zhishi), of which berberine and naringin are the main constituents. Though DZF has been clinically used for treatment of IR and metabolic syndrome for decades, its mechanism in vivo remains unknown. In the present study, we observed that both DZF and metformin, the first-line drug for type 2 diabetes, ameliorated insulin resistance with significant improvement of oral glucose tolerance test (OGTT) and homeostasis model assessment of IR (HOMA-IR) level in diabetic C57BL/Ksj-Lepr db -/- ( db/db ) mice...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29580688/sirt3-aggravates-metformin-induced-energy-stress-and-apoptosis-in-ovarian-cancer-cells
#14
Yao Wu, Wei-Nan Gao, Ya-Nan Xue, Li-Chao Zhang, Juan-Juan Zhang, Sheng-Yao Lu, Xiao-Yu Yan, Hui-Mei Yu, Jing Su, Lian-Kun Sun
Increasing evidence suggests that mitochondrial respiratory chain complex I participates in carcinogenesis and cancer progression by providing energy and maintaining mitochondrial function. However, the role of complex I in ovarian cancer is largely unknown. In this study we showed that metformin, considered to be an inhibitor of complex I, simultaneously inhibited cell growth and induced mitochondrial-related apoptosis in human ovarian cancer cells. Metformin interrupted cellular energy metabolism mainly by causing damage to complex I that impacted mitochondrial function...
March 23, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29579593/amp-activated-protein-kinase-protects-against-necroptosis-via-regulation-of-keap1-pgam5-complex
#15
Yi-Shu Wang, Peng Yu, Yong Wang, Jing Zhang, Wei Hang, Zhi-Xian Yin, Gang Liu, Jianfeng Chen, Kaitlin D Werle, Cheng-Shi Quan, Hang Gao, Qinghua Zeng, Rutao Cui, Jiyong Liang, Qiang Ding, Yu-Lin Li, Zhi-Xiang Xu
BACKGROUND: The AMP-activated protein kinase (AMPK) plays critical roles in growth regulation and metabolism reprogramming. AMPK activation protects cells against apoptosis from injury in different cell and animal models. However, its function in necroptosis remains largely unclear. METHODS AND RESULTS: In the current study, we demonstrated that AMPK was activated upon necroptosis induction and protected mouse embryonic fibroblasts (MEFs) and cardiomyocytes from N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and reactive oxygen species (ROS) induced necroptosis...
May 15, 2018: International Journal of Cardiology
https://www.readbyqxmd.com/read/29555409/functional-organic-cation-transporters-mediate-osteogenic-response-to-metformin-in-human-umbilical-cord-mesenchymal-stromal-cells
#16
Faisal E Al Jofi, Tao Ma, Dong Guo, Monica P Schneider, Yan Shu, Hockin H K Xu, Abraham Schneider
BACKGROUND: Compelling evidence indicates that metformin, a low-cost and safe orally administered biguanide prescribed to millions of type 2 diabetics worldwide, induces the osteoblastic differentiation of mesenchymal stromal cells (MSCs) through the 5' adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway. As a highly hydrophilic cationic compound, metformin uptake is facilitated by cell membrane organic cation transporters (OCTs) of the solute carrier 22A gene family...
March 16, 2018: Cytotherapy
https://www.readbyqxmd.com/read/29554968/metformin-induces-autophagy-and-g0-g1-phase-cell-cycle-arrest-in-myeloma-by-targeting-the-ampk-mtorc1-and-mtorc2-pathways
#17
Yan Wang, Wenbin Xu, Zixun Yan, Weili Zhao, Jianqing Mi, Junmin Li, Hua Yan
BACKGROUND: Metformin is a commonly used drug for the treatment of diabetes. Accumulating evidence suggests that it exerts anti-tumor effects in many cancers, including multiple myeloma (MM); however, the underlying molecular mechanisms have not been clearly elucidated. METHODS: The anti-myeloma effects of metformin were evaluated using human MM cell lines (RPMI8226 and U266) in vitro and in vivo NOD-SCID murine xenograft MM model. Cell viability was assessed with CCK8 and cell proliferation was measured by EdU incorporation assay...
March 20, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29540537/metformin-inhibits-inflammatory-signals-in-the-gut-by-controlling-ampk-and-p38-map-kinase-activation
#18
Davide Di Fusco, Vincenzo Dinallo, Ivan Monteleone, Federica Laudisi, Irene Marafini, Eleonora Franzè, Antonio Di Grazia, Rami Dwairi, Alfredo Colantoni, Angela Ortenzi, Carmine Stolfi, Giovanni Monteleone
Metformin, a hypoglycemic drug used for treatment of type 2 diabetes, regulates also inflammatory pathways. By using several models of intestinal inflammation, we examined whether metformin exerts anti-inflammatory effects and investigated the basic mechanism by which metformin blocks pathologic signals. Colitic mice given metformin exhibited less colonic inflammation and increased expression of active AMP-activated protein kinase, a mediator of the metabolic effects of metformin, in both epithelial and lamina propria compartments...
March 14, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29535569/the-improving-effect-of-hl271-a-chemical-derivative-of-metformin-a-popular-drug-for-type-ii-diabetes-mellitus-on-aging-induced-cognitive-decline
#19
Eunyoung Bang, Boyoung Lee, Joon-Oh Park, Yooncheol Jang, Aekyong Kim, Sungwuk Kim, Hee-Sup Shin
In recent years, as the aging population grows, aging-induced cognitive impairments including dementia and Alzheimer's disease (AD) have become the biggest challenges for global public health and social care. Therefore, the development of potential therapeutic drugs for aging-associated cognitive impairment is essential. Metabolic dysregulation has been considered to be a key factor that affects aging and dementia. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a primary sensor of cellular energy states and regulates cellular energy metabolism...
February 2018: Experimental Neurobiology
https://www.readbyqxmd.com/read/29526538/activation-of-ampk-inhibits-inflammatory-response-during-hypoxia-and-reoxygenation-through-modulating-jnk-mediated-nf-%C3%AE%C2%BAb-pathway
#20
Xu Chen, Xuan Li, Wenyan Zhang, Jie He, Bo Xu, Bin Lei, Zhenhua Wang, Courtney Cates, Thomas Rousselle, Ji Li
BACKGROUND: AMP-activated Protein Kinase (AMPK) is a stress-activated kinase that protects against cardiomyocyte injury during ischemia and reperfusion. c-Jun N-terminal kinase (JNK), a mitogen activated protein kinase, is activated by ischemia and reperfusion. NF-κB is an important transcription factor involved in ischemia and reperfusion injury. METHODS AND RESULTS: The intrinsic activation of AMPK attenuates the inflammation which occurred during ischemia/reperfusion through the modulation of the JNK mediated NF-κB signaling pathway...
March 8, 2018: Metabolism: Clinical and Experimental
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