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https://www.readbyqxmd.com/read/28444922/regulation-of-organelle-function-by-metformin
#1
REVIEW
Jeongho Kim, Young-Jai You
Metformin ameliorates hyperglycemia without the side effects of lactic acidosis or hypoglycemia. Metformin lowers the blood glucose level by decreasing hepatic glucose production in the liver and by increasing glucose uptake in the muscle. Recent studies show that metformin induces cell death in certain cancer cell lines by interfering with the metabolism of the cancer cells. Therefore, understanding the mechanisms of action for metformin will provide insights into how to better treat diabetes and other metabolic disorders and also into the development of new therapeutic drugs...
April 26, 2017: IUBMB Life
https://www.readbyqxmd.com/read/28444639/metformin-and-prostate-cancer-a-new-role-for-an-old-drug
#2
REVIEW
Jessica Whitburn, Claire M Edwards, Prasanna Sooriakumaran
PURPOSE OF REVIEW: Since epidemiological studies first demonstrated a potential positive effect of metformin in reducing cancer incidence and mortality, there has been an increased interest in not only better understanding metformin's mechanisms of action but also in exploring its potential anti-cancer effects. In this review, we aim to summarise the current evidence exploring a role for metformin in prostate cancer therapy. RECENT FINDINGS: Preclinical studies have demonstrated a number of antineoplastic biological effects via a range of molecular mechanisms...
June 2017: Current Urology Reports
https://www.readbyqxmd.com/read/28436023/activation-of-amp-activated-protein-kinase-by-metformin-ablates-angiotensin-ii-induced-endoplasmic-reticulum-stress-and-hypertension-in-mice-in-vivo
#3
Quanlu Duan, Ping Song, Ye Ding, Ming-Hui Zou
BACKGROUND AND PURPOSE: Metformin, one of the most frequently prescribed medications for type 2 diabetes, reportedly exerts blood pressure (BP)-lowering effects in patients with diabetes; however, the effects and underlying mechanisms of metformin on BP in non-diabetic condition remains to be determined. The aim of the present study was to determine the effects of metformin on angiotensin II (Ang II) infusion-induced hypertension in vivo. EXPERIMENTAL APPROACH: The effects of metformin on BP were investigated in wild-type (WT, C57BL/6 J) and AMP-activated protein kinase (AMPKα2) knockout (AMPKα2(-/-) ) mice with or without Ang II-infusion...
April 23, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28434975/protection-of-pc12%C3%A2-cells-from-cocaine-induced-cell-death-by-inhibiting-mitochondrial-permeability-transition
#4
Frederic Lamarche, Cecile Cottet-Rousselle, Luc Barret, Eric Fontaine
Cocaine abuse induces brain injury and neurodegeneration by a mechanism that has not yet been fully elucidated. Mitochondria play a key role in cell death processes, notably through the opening of the permeability transition pore (PTP). In this work, we examined the involvement of the PTP in cocaine-induced toxicity in PC12 cell lines. We used two different PTP inhibitors -i.e. cyclosporin A (CsA) and metformin-to assess their ability to counteract the cocaine induced effects. We first observed that a 48 h exposure to cocaine strongly sensitized cells to calcium overload, as measured by the calcium retention capacity...
April 20, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28433886/controlled-release-of-metformin-from-chitosan-based-nanocomposite-films-containing-mesoporous-mcm-41-nanoparticles-as-novel-drug-delivery-systems
#5
Zahra Shariatinia, Zahra Zahraee
Biocompatible nanocomposite films based on blended chitosan and poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (BP) polymers containing metformin (MET) drug and MCM-41 or MCM-41-APS (APS=aminopropylsilane) nanoparticles (NPs) were designed and fabricated in order to prepare novel drug delivery systems which are useful for controlled drug release purposes. The total pore volume and mesopore volume of MCM-41 were measured equal to 1.08 and 1.05 cm(3)/g but those of MCM-41-APS were 0...
April 13, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/28429253/modified-metformin-as-a-more-potent-anticancer-drug-mitochondrial-inhibition-redox-signaling-antiproliferative-effects-and-future-epr-studies
#6
Balaraman Kalyanaraman, Gang Cheng, Micael Hardy, Olivier Ouari, Adam Sikora, Jacek Zielonka, Michael B Dwinell
Metformin, one of the most widely prescribed antidiabetic drugs in the world, is being repurposed as a potential drug in cancer treatment. Epidemiological studies suggest that metformin exerts anticancer effects in diabetic patients with pancreatic cancer. However, at typical antidiabetic doses the bioavailability of metformin is presumably too low to exert antitumor effects. Thus, more potent analogs of metformin are needed in order to increase its anticancer efficacy. To this end, a new class of mitochondria-targeted metformin analogs (or mito-metformins) containing a positively-charged lipophilic triphenylphosphonium group was synthesized and tested for their antitumor efficacy in pancreatic cancer cells...
April 21, 2017: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28423712/model-based-unsupervised-learning-informs-metformin-induced-cell-migration-inhibition-through-an-ampk-independent-mechanism-in-breast-cancer
#7
Arjun P Athreya, Krishna R Kalari, Junmei Cairns, Alan J Gaglio, Quin F Wills, Nifang Niu, Richard Weinshilboum, Ravishankar K Iyer, Liewei Wang
We demonstrate that model-based unsupervised learning can uniquely discriminate single-cell subpopulations by their gene expression distributions, which in turn allow us to identify specific genes for focused functional studies. This method was applied to MDA-MB-231 breast cancer cells treated with the antidiabetic drug metformin, which is being repurposed for treatment of triple-negative breast cancer. Unsupervised learning identified a cluster of metformin-treated cells characterized by a significant suppression of 230 genes (p-value < 2E-16)...
March 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414668/autoimmune-diabetes-presented-with-diabetic-ketoacidosis-induced-by-immunotherapy-in-an-adult-with-melanoma
#8
A A Alzenaidi, J Dendy, L Rejjal
INTRODUCTION: Immunotherapy has been approved for treatment of melanoma. Autoimmune endocrinopathies have been reported in trials involving immunotherapy but autoimmune diabetes has not been definitively linked to them. Here we describe a case of autoimmune diabetes presenting with DKA after receiving combined immunotherapy with anti-CTLA4 and anti-PD1 monoclonal antibodies. CASE: A 47year old gentleman with metastatic melanoma presented to our institution with confusion, abdominal pain and decreased oral intake...
March 2017: Journal of the Louisiana State Medical Society: Official Organ of the Louisiana State Medical Society
https://www.readbyqxmd.com/read/28413172/the-effects-of-metformin-on-fibroblast-growth-factor-19-21-and-fibroblast-growth-factor-receptor-1-in-high-fat-diet-and-streptozotocin-induced-diabetic-rats
#9
Yan Wang, Ningning Dang, Pei Sun, Jin Xia, Chunxue Zhang, Shuguang Pang
To understand metformin’s effects on fibroblast growth factors (FGFs) and fibroblast growth factor receptor 1 (FGFR1), we investigated circulating fibroblast growth factor-19 (FGF19), FGF21 levels, and FGFR1 in type 2 diabetes mellitus (T2DM). In addition, protein kinase B (Akt) signaling pathway was detected to explain the possible mechanisms. T2DM was induced by feeding rats with high-fat diet for 11 weeks, followed by a low dose of streptozotocin (STZ, 30-35 mg/kg, intraperitoneally). Control rats (Con) were fed on a normal chow; diabetic rats (DM) were fed on high-fat diet supplemented with or without metformin (METF) for 12 weeks (500 mg・kg(-1)・d(-1))...
April 11, 2017: Endocrine Journal
https://www.readbyqxmd.com/read/28411689/moutan-cortex-and-paeoniae-radix-rubra-reverse-high-fat-diet-induced-metabolic-disorder-and-restore-gut-microbiota-homeostasis
#10
Ling-Jun Zhong, Zhi-Sheng Xie, Hua Yang, Ping Li, Xiao-Jun Xu
The present study was designed to investigate the therapeutic effcts of Moutan Cortex (CM, root bark of Paeonia suffruticosa Andr) and Paeoniae Radix Rubra (PR, root of Paeonia veitchii Lynch) on metabolic disorders, focusing on the infuence of CM and PR on the obesity-related gut microbiota homeostasis. The diet-induced obese (DIO) mouse model was used to test the therapeutic effects of CM and PR. The mice were orally administered with CM and PR for 6 weeks, and oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed to evaluate the insulin sensitivity of the mice...
March 2017: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/28410530/metformin-attenuated-endotoxin-induced-acute-myocarditis-via-activating-ampk
#11
Gang Liu, Kejia Wu, Li Zhang, Jie Dai, Wei Huang, Ling Lin, Pu Ge, Fuling Luo, Han Lei
Metformin is a widely used anti-diabetic drug and increasing evidence suggests that metformin have profound cardioprotective effects under both diabetic and non-diabetic situations. The protective benefits of metformin have been proved in diabetic patients with cardiovascular complications and in experimental animals with myocardial infarction and cardiac hypertrophy. In the present study, we found that treatment with metformin inhibited the cardiac expression of pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β) and interleukin 6 (IL-6) in endotoxin-challenged mice...
April 11, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28407669/metformin-inhibits-n-methyl-n-nitrosourea-induced-gastric-tumorigenesis-in-db-db-mice
#12
Shan Zhuang, Yongmei Jian, Yongning Sun
Type 2 diabetes can elevate risk of gastric cancer and metformin, an anti-diabetic agent, has an inhibitory effect against gastric cancer cell in vitro. However, the effect of metformin on type 2 diabetes-related gastric tumorigenesis in vivo is still not clear. In the present study, we aim to detect whether metformin can inhibit increased risk of gastric cancer in diabetic db/db mice and which the potential anti-cancer mechanisms of metformin are. 4-week-old mice were divided into 3 groups (2 db/db mice groups and one wild type mice group)...
April 13, 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28406985/metformin-inhibited-esophageal-squamous-cell-carcinoma-proliferation-in-vitro-and-in-vivo-and-enhanced-the-anti-cancer-effect-of-cisplatin
#13
Feng Wang, Xianfei Ding, Tao Wang, Zhengzheng Shan, Jun Wang, Shaoxuan Wu, Yanyan Chi, Yana Zhang, Zhuan Lv, Liuxing Wang, Qingxia Fan
Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy with poor prognosis in China. Chemotherapy now is one of the most frequently used treatments for patients with ESCC in middle or late stage, however the effects were often limited by increased chemoresistance or treatment toxicity. So it is urgent to find new drugs to treat ESCC patients. Metformin with low cost and toxicity has proved to have anti-cancer effects in a numerous cancers, while its role and mechanism in ESCC has seldom been studied...
2017: PloS One
https://www.readbyqxmd.com/read/28399491/metformin-and-improved-treatment-outcomes-in-radiation-therapy-a-review
#14
REVIEW
Nur Atiqah Binte Samsuri, Michelle Leech, Laure Marignol
BACKGROUND: Metformin, a primary treatment for diabetes mellitus (DM) patients, is associated with improved outcomes for diabetic cancer patients fuelling further investigation on its mechanisms of action. The radiosensitising properties of metformin are increasingly reported in pre-clinical studies. This review discusses whether metformin should be offered to radiotherapy (RT) cancer patients as a means to improve their treatment outcomes. MATERIALS AND METHODS: A database search was conducted for articles published with metformin as the main intervention between 2010 and 2016...
March 22, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28393220/metformin-increases-sensitivity-of-osteosarcoma-stem-cells-to-cisplatin-by-inhibiting-expression-of-pkm2
#15
Depeng Shang, Ju Wu, Lianyi Guo, Yanju Xu, Lezi Liu, Jianmin Lu
Multiple drug resistance is reported to be a major obstacle in treatment of osteosarcoma (OS). Research has demonstrated that small subsets of cells called cancer stem cells (CSCs) are responsible for multiple drug resistance. CSCs are potential targets for reversing chemoresistance. In the present study, we compared cisplatin sensitivity between OS stem cells and OS non-stem cells. We confirmed that OS stem cells showed significant cisplatin-resistance compared with the OS non-CSCs. Mechanically, we proved that overexpression of the pyruvate kinase isoenzyme M2 (PKM2) was responsible for the resistance to cisplatin in OS stem cells...
May 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28392962/anti-diabetic-effects-of-an-ethanol-extract-of-cassia-abbreviata-stem-bark-on-diabetic-rats-and-possible-mechanism-of-its-action-anti-diabetic-properties-of-cassia-abbreviata
#16
Keagile Bati, Tebogo Elvis Kwape, Padmaja Chaturvedi
OBJECTIVES: This study aimed to evaluate the hypoglycemic effects of an ethanol extract of Cassia abbreviata (ECA) bark and the possible mechanisms of its action in diabetic albino rats. METHODS: ECA was prepared by soaking the powdered plant material in 70% ethanol. It was filtered and made solvent-free by evaporation on a rotary evaporator. Type 2 diabetes was induced in albino rats by injecting 35 mg/kg body weight (bw) of streptozotocin after having fed the rats a high-fat diet for 2 weeks...
March 2017: Journal of Pharmacopuncture
https://www.readbyqxmd.com/read/28389241/inhibition-of-src-homology-2-domain-containing-protein-tyrosine-phosphatase-as-the-possible-mechanism-of-metformin-assisted-amelioration-of-obesity-induced-insulin-resistance-in-high-fat-diet-fed-c57bl-6j-mice
#17
Yadhu Sharma, Samina Bashir, Ansarullah, Mohemmed Faraz Khan, Altaf Ahmad, Farah Khan
SHP-1 (Src homology 2 domain containing protein tyrosine phosphatase) is a known negative regulator of insulin signaling and inflammation. To date, the molecular mechanism of metformin in modulating SHP-1 expression has remained elusive. In the present study, we have investigated the role of SHP-1 in relation to anti-hyperglycemic and anti-inflammatory actions of metformin in an obese phenotype mouse model. We observed that metformin treatment significantly reduced SHP-1 activity in obese mice, leading to improved insulin sensitivity...
May 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28386373/mechanism-of-progestin-resistance-in-endometrial-precancer-cancer-through-nrf2-survivin-pathway
#18
Rujia Fan, Yiying Wang, Yue Wang, Li Wei, Wenxin Zheng
Progestin is commonly used for young patients suffering from endometrial hyperplasia or cancer. However, there is approximately 30% failure rate with unclear mechanism. We investigated if Nrf2-survivin pathway contributes the progestin resistance (PR) in this setting. Current study detected Nrf2 and survivin protein expression in post progestin treated endometrial tissue samples by using immunohistochemistry. Transfection of Nrf2 and survivin into endometrial cancer cells in vitro was done to determine the roles of Nrf2 and survivin in progestin resistance...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28385910/metformin-reduces-prostate-tumor-growth-in-a-diet-dependent-manner-by-modulating-multiple-signaling-pathways
#19
Andre Sarmento-Cabral, Fernando L-Lopez, Manuel D Gahete, Justo P Castano, Raul M Luque
Prostate-cancer is strongly influenced by obesity, wherein metformin could represent a promising treatment; however, the endocrine-metabolic/cellular/molecular-mechanisms underlying these associations and effects are still unclear. To determine the beneficial anti-tumoral effects of metformin on prostate-cancer progression/aggressiveness and the relative contribution of high-fat diet (HFD; independently of obesity), we used HFD-fed immuno-suppressed mice inoculated with PC3 cells (which exhibited partial resistance to diet-induced obesity) compared with low-fat diet (LFD)-fed control-mice...
April 6, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28384260/denv-up-regulates-the-hmg-coa-reductase-activity-through-the-impairment-of-ampk-phosphorylation-a-potential-antiviral-target
#20
Rubén Soto-Acosta, Patricia Bautista-Carbajal, Margot Cervantes-Salazar, Antonio H Angel-Ambrocio, Rosa M Del Angel
Dengue is the most common mosquito-borne viral disease in humans. Changes of lipid-related metabolites in endoplasmic reticulum of dengue virus (DENV) infected cells have been associated with replicative complexes formation. Previously, we reported that DENV infection inhibits HMGCR phosphorylation generating a cholesterol-enriched cellular environment in order to favor viral replication. In this work, using enzymatic assays, ELISA, and WB we found a significant higher activity of HMGCR in DENV infected cells, associated with the inactivation of AMPK...
April 2017: PLoS Pathogens
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