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AMPK AND metformin

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https://www.readbyqxmd.com/read/28644886/complex-i-inhibition-augments-dichloroacetate-cytotoxicity-through-enhancing-oxidative-stress-in-vm-m3-glioblastoma-cells
#1
Nathan P Ward, Angela M Poff, Andrew P Koutnik, Dominic P D'Agostino
The robust glycolytic metabolism of glioblastoma multiforme (GBM) has proven them susceptible to increases in oxidative metabolism induced by the pyruvate mimetic dichloroacetate (DCA). Recent reports demonstrate that the anti-diabetic drug metformin enhances the damaging oxidative stress associated with DCA treatment in cancer cells. We sought to elucidate the role of metformin's reported activity as a mitochondrial complex I inhibitor in the enhancement of DCA cytotoxicity in VM-M3 GBM cells. Metformin potentiated DCA-induced superoxide production, which was required for enhanced cytotoxicity towards VM-M3 cells observed with the combination...
2017: PloS One
https://www.readbyqxmd.com/read/28642704/quercetin-a-lead-compound-against-type-2-diabetes-ameliorates-glucose-uptake-via-ampk-pathway-in-skeletal-muscle-cell-line
#2
R Dhanya, A D Arya, P Nisha, P Jayamurthy
Herein we investigated the molecular mechanism of action of the citrus flavonoid, quercetin in skeletal muscle cells (L6 myotubes). Taking advantage of protein kinase inhibitors, we proved that the effect of quercetin on 2-NBDG uptake in L6 myotubes was not through insulin signaling pathway, but through adenosine monophosphate kinase (AMPK) pathway and its downstream target p38 MAPK. An increase in the cellular AMP to ATP ratio on pretreatment may account for AMPK activation which was coupled with a transient change in mitochondrial membrane potential...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28638078/the-stress-response-factor-daf-16-foxo-is-required-for-multiple-compound-families-to-prolong-the-function-of-neurons-with-huntington-s-disease
#3
Francesca Farina, Emmanuel Lambert, Lucie Commeau, François-Xavier Lejeune, Nathalie Roudier, Cosima Fonte, J Alex Parker, Jacques Boddaert, Marc Verny, Etienne-Emile Baulieu, Christian Neri
Helping neurons to compensate for proteotoxic stress and maintain function over time (neuronal compensation) has therapeutic potential in aging and neurodegenerative disease. The stress response factor FOXO3 is neuroprotective in models of Huntington's disease (HD), Parkinson's disease and motor-neuron diseases. Neuroprotective compounds acting in a FOXO-dependent manner could thus constitute bona fide drugs for promoting neuronal compensation. However, whether FOXO-dependent neuroprotection is a common feature of several compound families remains unknown...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634570/to-use-or-not-to-use-metformin-in-cerebral-ischemia-a-review-of-the-application-of-metformin-in-stroke-rodents
#4
REVIEW
Isaac Arbeláez-Quintero, Mauricio Palacios
Ischemic strokes are major causes of death and disability. Searching for potential therapeutic strategies to prevent and treat stroke is necessary, given the increase in overall life expectancy. Epidemiological reports indicate that metformin is an oral antidiabetic medication that can reduce the incidence of ischemic events in patients with diabetes mellitus. Its mechanism of action has not been elucidated, but metformin pleiotropic effects involve actions in addition to glycemic control. AMPK activation has been described as one of the pharmacological mechanisms that explain the action of metformin and that lead to neuroprotective effects...
2017: Stroke Research and Treatment
https://www.readbyqxmd.com/read/28632780/metformin-intake-associates-with-better-cognitive-function-in-patients-with-huntington-s-disease
#5
David Hervás, Victoria Fornés-Ferrer, Ana Pilar Gómez-Escribano, María Dolores Sequedo, Carmen Peiró, José María Millán, Rafael P Vázquez-Manrique
Huntington's disease (HD) is an inherited, dominant neurodegenerative disorder caused by an abnormal expansion of CAG triplets in the huntingtin gene (htt). Despite extensive efforts to modify the progression of HD thus far only symptomatic treatment is available. Recent work suggests that treating invertebrate and mice HD models with metformin, a well-known AMPK activator which is used worldwide to treat type 2-diabetes, reduces mutant huntingtin from cells and alleviates many of the phenotypes associated to HD...
2017: PloS One
https://www.readbyqxmd.com/read/28628912/liver-kinase-b1-amp-activated-protein-kinase-pathway-activation-attenuated-the-progression-of-endotoxemia-in-the-diabetic-mice
#6
Yan Yang, Ruolan Dong, Danli Hu, Zhihui Chen, Menglu Fu, Dao Wen Wang, Xizhen Xu, Ling Tu
BACKGROUND/AIMS: Sepsis is a common disease that continues to increase in prevalence worldwide, and diabetes mellitus may make the situation worse. This study was designed to determine the role of Liver Kinase B1 (LKB1)/adenosine monophosphate-activated protein kinase (AMPK) signaling pathway in diabetic mice complicated with systemic endotoxemia. METHODS: The effects of LKB1/AMPK signaling pathway activation on endotoxemia were investigated in streptozotocin induced diabetic mice (STZ-mice) and db/db diabetic mice...
June 19, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28621668/blocking-epithelial-to-mesenchymal-transition-in-glioblastoma-with-a-sextet-of-repurposed-drugs-the-eis-regimen
#7
Richard E Kast, Nicolas Skuli, Georg Karpel-Massler, Guido Frosina, Timothy Ryken, Marc-Eric Halatsch
This paper outlines a treatment protocol to run alongside of standard current treatment of glioblastoma- resection, temozolomide and radiation. The epithelial to mesenchymal transition (EMT) inhibiting sextet, EIS Regimen, uses the ancillary attributes of six older medicines to impede EMT during glioblastoma. EMT is an actively motile, therapy-resisting, low proliferation, transient state that is an integral feature of cancers' lethality generally and of glioblastoma specifically. It is believed to be during the EMT state that glioblastoma's centrifugal migration occurs...
June 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28621447/metformin-prevents-vascular-prostanoid-release-alterations-induced-by-a-high-fat-diet-in-rats
#8
H J Lee, S M Cantú, A S Donoso, M R Choi, H A Peredo, A M Puyó
Perivascular adipose tissue dysfunction induced by high-fat feeding leads to alterations in the modulation of inflammation, contractile activity of the vascular smooth muscle and endothelial function, all risk factors in the development of hypertension. Metformin, an activator of AMP-activated protein kinase (AMPK), is currently the first-line drug treatment for type 2 diabetes (T2DM) and metabolic syndrome. Besides its glucose-lowering effect, there is an interest in actions of this drug with potential relevance in cardiovascular diseases...
June 16, 2017: Autonomic & Autacoid Pharmacology
https://www.readbyqxmd.com/read/28618116/differences-in-p53-status-significantly-influence-the-cellular-response-and-cell-survival-to-1-25-dihydroxyvitamin-d3-metformin-cotreatment-in-colorectal-cancer-cells
#9
Mohamed A Abu El Maaty, Wendy Strassburger, Tooba Qaiser, Yasamin Dabiri, Stefan Wölfl
Mutations in the tumor suppressor p53 are highly prevalent in cancers and are known to influence the sensitivity of cells to various chemotherapeutics including the anti-cancer candidates 1,25-dihydrovitamin D3 [1,25D3] and metformin. Previous studies have demonstrated additive/synergistic anti-cancer effects of the 1,25D3-metformin combination in different models, however the influence of p53 status on the efficacy of this regimen has not been investigated. The CRC cell lines HCT116 wild-type (wt), HCT116 p53-/- and HT-29 (mutant; R273H) were employed, covering 3 different p53 variations...
June 15, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28614117/role-of-amp-activated-protein-kinase-in-kidney-tubular-transport-metabolism-and-disease
#10
Roshan Rajani, Nuria M Pastor-Soler, Kenneth R Hallows
PURPOSE OF REVIEW: AMP-activated protein kinase (AMPK) is a metabolic sensor that regulates cellular energy balance, transport, growth, inflammation, and survival functions. This review explores recent work in defining the effects of AMPK on various renal tubular epithelial ion transport proteins as well as its role in kidney injury and repair in normal and disease states. RECENT FINDINGS: Recently, several groups have uncovered additional functions of AMPK in the regulation of kidney and transport proteins...
June 12, 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/28611100/ampk-activation-enhances-the-anti-atherogenic-effects-of-high-density-lipoproteins-in-apoe-mice
#11
Ang Ma, Jing Wang, Liu Yang, Yuanyuan An, Haibo Zhu
HDL plays crucial roles at multiple stages of the pathogenesis of atherosclerosis. AMP-activated protein kinase (AMPK) is a therapeutic candidate for the treatment of cardiovascular disease. However, the effect of AMPK activation on HDL functionality has not been established in vivo. We assessed the effects of pharmacological AMPK activation using A-769662, AICAR, metformin, and IMM-H007 on the atheroprotective functions of HDL in apoE-deficient (apoE-/-) mice fed with a high fat diet. After administration, although there no changes in serum lipid levels among the groups...
June 13, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28606032/metformin-a-new-era-for-an-old-drug-in-the-treatment-of-immune-mediated-disease
#12
Mark Schuiveling, Nadia Vazirpanah, Timothy R D J Radstake, Maili Zimmermann, Jasper C A Broen
Metformin, a widely prescribed blood glucose normalizing antidiabetic drug, is now beginning to receive increasing attention due to its potential anti-inflammatory properties. Metformin suppresses immune responses mainly through its direct effect on the cellular functions of various immune cell types by induction of AMPK and subsequent inhibition of mTORC1, and by inhibition of mitochondrial ROS production. Among key immune events, this results in inhibited monocyte to macrophage differentiation and restrained inflammatory capacity of activated macrophages...
June 12, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28589443/metformin-a-future-therapy-for-neurodegenerative-diseases
#13
REVIEW
Magdalena Markowicz-Piasecka, Joanna Sikora, Aleksandra Szydłowska, Agata Skupień, Elżbieta Mikiciuk-Olasik, Kristiina M Huttunen
Type 2 diabetes mellitus (T2DM) is a complex, chronic and progressive metabolic disease, which is characterized by relative insulin deficiency, insulin resistance, and high glucose levels in blood. Esteemed published articles and epidemiological data exhibit an increased risk of developing Alzheimer's disease (AD) in diabetic pateints. Metformin is the most frequently used oral anti-diabetic drug, which apart from hypoglycaemic activity, improves serum lipid profiles, positively influences the process of haemostasis, and possesses anti-inflammatory properties...
June 6, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28581641/clk1-regulated-aerobic-glycolysis-is-involved-in-gliomas-chemoresistance
#14
Li Zhang, Huicui Yang, Wenbin Zhang, Zhongqin Liang, Qiang Huang, Guoqiang Xu, Xuechu Zhen, Long Tai Zheng
Chemoresistance remains a major challenge for the treatment of glioma. In the present study, we investigated the role of Clk1, which encodes an enzyme that is necessary for ubiquinone biosynthesis in glioma chemoresistance in vitro. The results showed that Clk1 was highly expressed in GL261 mouse glioma cells which were most sensitive to BCNU while was expressed in BCNU resistant cells such as glioma cancer stem cells: T98G, U87MG and U251 glioma cells at low levels. Knockdown of Clk1 in GL261 glioma cells significantly reduced BCNU- or cisplatin- induced cell apoptosis whereas the proliferative activity and the expression of multi-drug resistance -related genes including MDR1, MGMT and GSTP1 were not changed...
June 5, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28580793/rationale-and-protocol-of-metnet-2-trial-lanreotide-autogel-plus-metformin-in-advanced-gastrointestinal-or-lung-neuroendocrine-tumors
#15
Sara Pusceddu, Natalie Prinzi, Giuseppe Lo Russo, Daniela Femia, Massimo Milione, Federica Perrone, Elena Tamborini, Laura Concas, Iolanda Pulice, Claudio Vernieri, Francesca Corti, Roberto Buzzoni, Filippo de Braud
Metformin (MET) has recently emerged as a potentially active agent in cancer prevention and treatment. MET is thought to exert its antitumor effects either via modification of systemic metabolism or through cell-autonomous effects (e.g., activation of AMPK and inhibition of the mTOR pathway). Preliminary findings of the PRIME-NET study suggest that the addition of MET to treatment with everolimus (EVE) and/or somatostatin analogs (SSAs) can provide clinical benefit in diabetic neuroendocrine tumor (NET) patients...
June 5, 2017: Future Oncology
https://www.readbyqxmd.com/read/28580278/fgf21-does-not-require-adipocyte-amp-activated-protein-kinase-ampk-or-the-phosphorylation-of-acetyl-coa-carboxylase-acc-to-mediate-improvements-in-whole-body-glucose-homeostasis
#16
Emilio P Mottillo, Eric M Desjardins, Andreas M Fritzen, Vito Z Zou, Justin D Crane, Julian M Yabut, Bente Kiens, Derek M Erion, Adhiraj Lanba, James G Granneman, Saswata Talukdar, Gregory R Steinberg
OBJECTIVE: Fibroblast growth factor 21 (FGF21) shows great potential for the treatment of obesity and type 2 diabetes, as its long-acting analogue reduces body weight and improves lipid profiles of participants in clinical studies; however, the intracellular mechanisms mediating these effects are poorly understood. AMP-activated protein kinase (AMPK) is an important energy sensor of the cell and a molecular target for anti-diabetic medications. This work examined the role of AMPK in mediating the glucose and lipid-lowering effects of FGF21...
June 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28579909/the-alleviative-effects-of-metformin-for-lipopolysaccharide-induced-acute-lung-injury-rat-model-and-its-underlying-mechanism
#17
Xiangcheng Zhang, Futai Shang, Liangliang Hui, Kui Zang, Gengyun Sun
For patients who have sepsis, acute lung injury (ALI) causes most of death. Metformin (Met) is an anti-hyperglycemic agent and it has extensive pharmacological properties. This study aimed to analyze the influence of Met on lipopolysaccharide (LPS) -induced ALI. Met (1, 2, and 4 mg/kg) were injected and LPS was injected 30 min later. The data suggested Met can reduce release of inflammatory cytokines and bronchoalveolar lavage fluid (BALF) protein expression, reduce lung wet/dry ratio, and significantly improve LPS-induced lung destruction during ALI...
May 2017: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
https://www.readbyqxmd.com/read/28579457/metformin-ameliorates-gender-and-age-dependent-hemodynamic-instability-and-myocardial-injury-in-murine-hemorrhagic-shock
#18
Dzmitry Matsiukevich, Giovanna Piraino, Patrick Lahni, Paul W Hake, Vivian Wolfe, Michael O'Connor, Jeanne James, Basilia Zingarelli
Severity of multiple organ failure is significantly impacted by age and gender in patients with hemorrhagic shock. However, the molecular mechanisms underlying the enhanced organ injury are not fully understood. AMP-activated protein kinase (AMPK) is a pivotal orchestrator of metabolic responses during stress. We investigated whether hemorrhage-induced myocardial injury is age and gender dependent and whether treatment with metformin, an AMPK activator, affords cardioprotective effects. C57/BL6 young (3-5months) and mature (9-12months) male and female mice were subjected to hemorrhagic shock by blood withdrawing followed by resuscitation with blood and Lactated Ringer's solution...
June 1, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28571536/amp-activated-protein-kinase-as-a-drug-target-in-chronic-kidney-disease
#19
Soumaya Allouch, Shankar Munusamy
Chronic kidney disease (CKD) is a condition increasingly affecting millions of individuals worldwide and is ranked as the ninth leading cause of death in the United States. AMP-activated protein kinase (AMPK) is an energy sensor that plays a pivotal role in cellular homoeostasis. Deficiency in AMPK activity and autophagic signaling, and sustained activation of mammalian target of rapamycin (mTOR) and endoplasmic reticulum (ER) stress have been shown to promote epithelial-to-mesenchymal transition (EMT) and renal cell apoptosis and contribute to CKD...
June 1, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28560428/metformin-ameliorates-hepatic-steatosis-and-improves-the-induction-of-autophagy-in-hfd%C3%A2-induced-obese-mice
#20
Min Li, Antara Sharma, Chunyan Yin, Xinrui Tan, Yanfeng Xiao
The present study aimed to investigate the effect of metformin on the induction of autophagy in the liver and adipose tissues of a mouse model of obesity. C57BL/6J mice were fed a high‑fat diet (HFD) for 12 weeks to induce obesity‑associated hepatic steatosis, and treated with metformin (150 mg/kg/d) by intraperitoneal injection for the final 4 weeks of HFD feeding. Body weight was recorded weekly, and the food intake of the mice was recorded daily during the treatment period. Liver and adipose tissues were harvested for histological and molecular analyses...
July 2017: Molecular Medicine Reports
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