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https://www.readbyqxmd.com/read/28819951/metformin-a-new-old-drug
#1
Marta Patrycja Wróbel, Bogdan Marek, Dariusz Kajdaniuk, Dominika Rokicka, Aleksandra Szymborska-Kajanek, Krzysztof Strojek
For many years metformin has been the gold standard in the treatment of type 2 diabetes. According to recommendations of the most important diabetes associations, this is the first-choice drug for use as monotherapy in patients with newly diagnosed type 2 diabetes. Metformin is also recommended in combined treatment when monotherapy is no longer effective. It is then combined with a sulfony-lurea, an incretin, flozin, or insulin, irrespective of the number of insulin injections per day. Besides its properties used in the treatment of diabetes, metformin has been treated for some time as a drug of a so-called pleiotropic activity, as each year brings new reports about its favourable effect in different conditions...
2017: Endokrynologia Polska
https://www.readbyqxmd.com/read/28819383/metformin-inhibits-tumorigenesis-and-tumor-growth-of-breast-cancer-cells-by-upregulating-mir-200c-but-downregulating-akt2-expression
#2
Jiali Zhang, Gefei Li, Yuan Chen, Lei Fang, Chen Guan, Fumao Bai, Mengni Ma, Jianxin Lyu, Qing H Meng
Background: Metformin has been reported to inhibit the growth of various types of cancers, including breast cancer. Yet the mechanisms underlying the anticancer effects of metformin are not fully understood. Growing evidence suggests that metformin's anticancer effects are mediated at least in part by modulating microRNAs, including miR-200c, which has a tumor suppressive role in breast cancer. We hypothesized that miR-200c has a role in the antitumorigenic effects of metformin on breast cancer cells. Methods: To delineate the role of miR-200c in the effects of metformin on breast cancer, plasmids containing pre-miR-200c or miR-200c inhibitor were transfected into breast cancer cell lines...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819133/combined-transcriptome-and-metabolome-analyses-of-metformin-effects-reveal-novel-links-between-metabolic-networks-in-steroidogenic-systems
#3
Sameer S Udhane, Balazs Legeza, Nesa Marti, Damian Hertig, Gaëlle Diserens, Jean-Marc Nuoffer, Peter Vermathen, Christa E Flück
Metformin is an antidiabetic drug, which inhibits mitochondrial respiratory-chain-complex I and thereby seems to affect the cellular metabolism in many ways. It is also used for the treatment of the polycystic ovary syndrome (PCOS), the most common endocrine disorder in women. In addition, metformin possesses antineoplastic properties. Although metformin promotes insulin-sensitivity and ameliorates reproductive abnormalities in PCOS, its exact mechanisms of action remain elusive. Therefore, we studied the transcriptome and the metabolome of metformin in human adrenal H295R cells...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28817623/metformin-attenuates-myocardial-ischemia-reperfusion-injury-via-up-regulation-of-antioxidant-enzymes
#4
Xiaoling Wang, Lei Yang, Licheng Kang, Jing Li, Liang Yang, Jincai Zhang, Jie Liu, Mengmeng Zhu, Qiong Zhang, Yanna Shen, Zhi Qi
The objective was to examine the protective effect of metformin (Met) on myocardial ischemia-reperfusion (IR) injury and whether the mechanism was related to the AMPK/ antioxidant enzymes signaling pathway. Rat Langendorff test and H2O2-treated rat cardiomyocytes (H9c2) were used in this study. Met treatment significantly improved left ventricular (LV) function, reduced infarct size and CK-MB release in comparison with IR group. Decreased TUNEL staining positive cells were also observed in IR+Met group ex vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28809398/precision-medicine-for-suicidality-from-universality-to-subtypes-and-personalization
#5
A B Niculescu, H Le-Niculescu, D F Levey, P L Phalen, H L Dainton, K Roseberry, E M Niculescu, J O Niezer, A Williams, D L Graham, T J Jones, V Venugopal, A Ballew, M Yard, T Gelbart, S M Kurian, A Shekhar, N J Schork, G E Sandusky, D R Salomon
Suicide remains a clear, present and increasing public health problem, despite being a potentially preventable tragedy. Its incidence is particularly high in people with overt or un(der)diagnosed psychiatric disorders. Objective and precise identification of individuals at risk, ways of monitoring response to treatments and novel preventive therapeutics need to be discovered, employed and widely deployed. We sought to investigate whether blood gene expression biomarkers for suicide (that is, a 'liquid biopsy' approach) can be identified that are more universal in nature, working across psychiatric diagnoses and genders, using larger cohorts than in previous studies...
August 15, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28807678/metformin-lowers-%C3%AE-synuclein-phosphorylation-and-upregulates-neurotrophic-factor-in-the-mptp-mouse-model-of-parkinson-s-disease
#6
Nikita Katila, Sunil Bhurtel, Sina Shadfar, Sunil Srivastav, Sabita Neupane, Uttam Ojha, Gil-Saeng Jeong, Dong-Young Choi
In spite of the massive research for the identification of neurorestorative or neuroprotective intervention for curing Parkinson's disease (PD), there is still lack of clinically proven neuroprotective agents. Metformin, a common anti-hyperglycemic drug has been known to possess neuroprotective properties. However, specific mechanisms by which metformin protects neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity remain to be elucidated. In this study, we assessed the neuroprotective effects of metformin in the subchronic MPTP model of PD, and explored its feasible mechanisms for neuroprotection...
August 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28802138/inhibition-of-bioenergetic-metabolism-by-the-combination-of-metformin-and-2-deoxyglucose-highly-decreases-viability-of-feline-mammary-carcinoma-cells
#7
María Florencia Arbe, Chiara Fondello, Lucrecia Agnetti, Gabriel Martín Álvarez, Matías Nicolás Tellado, Gerardo Claudio Glikin, Liliana María Elena Finocchiaro, Marcela Solange Villaverde
Feline mammary carcinoma (FMC) is a highly aggressive pathology that has been proposed as an interesting model of breast cancer disease, especially for the hormone refractory subgroup. Recently, cancer cell metabolism has been described as a hallmark of cancer cells. Here, we investigate the effects and mechanism of metabolic modulation by metformin (MET, anti-diabetic drug), 2-deoxyglucose (2DG, hexokinase inhibitor) or a combination of both drugs, MET/2DG on two established FMC cells lines: AlRB (HER2 (3+) and Ki67<5%) and AlRATN (HER2 (-) and Ki67>15%)...
August 3, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28800931/molecular-signatures-of-longevity-insights-from-cross-species-comparative-studies
#8
REVIEW
Siming Ma, Vadim N Gladyshev
Much of the current research on longevity focuses on the aging process within a single species. Several molecular players (e.g. IGF1 and MTOR), pharmacological compounds (e.g. rapamycin and metformin), and dietary approaches (e.g. calorie restriction and methionine restriction) have been shown to be important in regulating and modestly extending lifespan in model organisms. On the other hand, natural lifespan varies much more significantly across species. Within mammals alone, maximum lifespan differs more than 100 fold, but the underlying regulatory mechanisms remain poorly understood...
August 8, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28795250/metformin-reduces-total-microparticles-and-microparticles-expressing-tissue-factor-in-women-with-polycystic-ovary-syndrome
#9
Laura M L Carvalho, Cláudia N Ferreira, Ana L Candido, Fernando M Reis, Mirelle O Sóter, Mariana F Sales, Ieda F O Silva, Fernanda F C Nunes, Karina Braga Gomes
PURPOSE: The objective of this study was to evaluate the levels of total microparticles (MPs) and microparticles-expressing tissue factor (TFMPs) in women with polycystic ovarian syndrome (PCOS) who use metformin comparing to those who do not take metformin. METHODS: We quantified total MPs and TFMPs in the plasma of 50 patients with PCOS-13 of these women used metformin (850 mg 2×/day during at least 6 months) and the other 37 did not. For this purpose, the microparticles (MPs) were purified by differential centrifugation of the plasma and, subsequently, by flow cytometry, using annexin-V and CD142 as markers...
August 9, 2017: Archives of Gynecology and Obstetrics
https://www.readbyqxmd.com/read/28794822/overview-of-glucagon-like-peptide-1-receptor-agonists-for-the-treatment-of-patients-with-type-2-diabetes
#10
Kelvin Lingjet Tran, Young In Park, Shalin Pandya, Navin John Muliyil, Brandon David Jensen, Kovin Huynh, Quang T Nguyen
BACKGROUND: It is estimated that 29.1 million people or 9.3% of the US population have diabetes, which contributes to considerable medical and financial burden. Type 2 diabetes mellitus is characterized by insulin resistance and insulin secretion impairment leading to hyperglycemia. The presence of insulin resistance is strongly correlated with obesity. OBJECTIVE: This article reviews the available glucagon-like peptide-1 (GLP-1) receptor agonists and their role in the management of patients with diabetes, to help guide the selection of the most suitable agent for the individualized treatment of patients with type 2 diabetes...
June 2017: American Health & Drug Benefits
https://www.readbyqxmd.com/read/28782285/metformin-enhances-doxorubicin-sensitivity-via-inhibition-of-doxorubicin-efflux-in-p-gp-overexpressing-mcf-7-cells
#11
Vahid Shafiei-Irannejad, Nasser Samadi, Bahman Yousefi, Roya Salehi, Kobra Velaei, Nosratollah Zarghami
Resistance against chemotherapy is still a major problem in successful cancer treatment in the clinic. Therefore, identifying new compounds with lower side effects and higher efficacy is an important approach to overcome multidrug resistance (MDR). Here, we investigated the activity and possible mechanism of the antidiabetic drug, metformin, in human doxorubicin (DOX) resistant breast cancer (MCF-7/DOX) cells. The effect of metformin on the cytotoxicity of DOX was evaluated by MTT assay. The P-gp mRNA/protein expression levels following treatment with metformin was determined using real time polymerase chain reaction (RT-PCR) and western blot analysis, respectively...
August 6, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28778047/metformin-treatment-significantly-enhances-intestinal-glucose-uptake-in-patients-with-type-2-diabetes-results-from-a-randomized-clinical-trial
#12
Jukka P Koffert, Kirsi Mikkola, Kirsi A Virtanen, Anna-Maria D Andersson, Linda Faxius, Kirsti Hällsten, Mikael Heglind, Letizia Guiducci, Tam Pham, Johanna M U Silvola, Jenni Virta, Olof Eriksson, Saila P Kauhanen, Antti Saraste, Sven Enerbäck, Patricia Iozzo, Riitta Parkkola, Maria F Gomez, Pirjo Nuutila
AIMS: Metformin therapy is associated with diffuse intestinal (18)F-fluoro-deoxyglucose (FDG) accumulation in clinical diagnostics using routine FDG-PET imaging. We aimed to study whether metformin induced glucose uptake in intestine is associated with the improved glycaemic control in patients with type 2 diabetes. Therefore, we compared the effects of metformin and rosiglitazone on intestinal glucose metabolism in patients with type 2 diabetes in a randomized placebo controlled clinical trial, and further, to understand the underlying mechanism, evaluated the effect of metformin in rats...
July 20, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28776376/new-evidence-for-the-mechanism-of-action-of-a-type-2-diabetes-drug-using-a-magnetic-bead-based-automated-biosensing-platform
#13
Rokon Uddin, Nur E Habiba, Graham Rena, En Te Hwu, Anja Boisen
The mechanism of action (MOA) of the first line type-2 diabetes drug metformin remains unclear despite its widespread usage. However, recent evidence suggests that the mitochondrial copper (Cu)-binding action of metformin may contribute towards the drug's MOA. Here, we present a novel biosensing platform for investigating the MOA of metformin using a magnetic microbead -based agglutination assay which has allowed us to demonstrate for the first time the interaction between Cu and metformin at clinically relevant low micromolar concentrations of the drug, thus suggesting a potential pathway of metformin's blood-glucose lowering action...
August 4, 2017: ACS Sensors
https://www.readbyqxmd.com/read/28776086/the-mechanisms-of-action-of-metformin
#14
REVIEW
Graham Rena, D Grahame Hardie, Ewan R Pearson
Metformin is a widely-used drug that results in clear benefits in relation to glucose metabolism and diabetes-related complications. The mechanisms underlying these benefits are complex and still not fully understood. Physiologically, metformin has been shown to reduce hepatic glucose production, yet not all of its effects can be explained by this mechanism and there is increasing evidence of a key role for the gut. At the molecular level the findings vary depending on the doses of metformin used and duration of treatment, with clear differences between acute and chronic administration...
August 3, 2017: Diabetologia
https://www.readbyqxmd.com/read/28776080/repurposing-metformin-for-the-prevention-of-cancer-and-cancer-recurrence
#15
REVIEW
Brandy M Heckman-Stoddard, Andrea DeCensi, Vikrant V Sahasrabuddhe, Leslie G Ford
Multiple epidemiological studies have documented an association between metformin, used for treatment of type 2 diabetes, and reduced cancer incidence and mortality. Cell line models may not accurately reflect the effects of metformin in the clinical setting. Moreover, findings from animal model studies have been inconsistent, whilst those from more recent epidemiological studies have tempered the overall effect size. The purpose of this review is to examine metformin's chemopreventive potential by outlining relevant mechanisms of action, the most recent epidemiologic evidence, and recently completed and ongoing clinical trials...
August 3, 2017: Diabetologia
https://www.readbyqxmd.com/read/28770331/the-pharmacogenetics-of-metformin
#16
REVIEW
Jose C Florez
Despite its widespread use as the first-line agent for the treatment of type 2 diabetes, it has become clear that metformin does not work optimally for everyone. Elucidating who are the likely metformin responders and non-responders is hampered by our limited knowledge of its precise molecular mechanism of action. One approach to achieve the related goals of stratifying patients into response subgroups and identifying the molecular targets of metformin involves the deployment of agnostic genome-wide approaches in cohorts of appropriate size to attain sufficient statistical power...
August 3, 2017: Diabetologia
https://www.readbyqxmd.com/read/28770330/metformin-therapy-for-the-reproductive-and-metabolic-consequences-of-polycystic-ovary-syndrome
#17
EDITORIAL
Susan Sam, David A Ehrmann
Polycystic ovary syndrome (PCOS), the most common hormonal disorder among women of reproductive age, has various metabolic and reproductive consequences. Metformin was originally shown to lower testosterone levels in women with PCOS in the 1990s, an effect presumably related to its insulin sensitising actions. However, the precise mechanisms of metformin action in PCOS remain unclear and there is considerable heterogeneity in the clinical response to this therapy in women with PCOS. Recent evidence indicates that genetic factors may play a significant role in predicting response to metformin therapy in PCOS and future studies are needed to further identify women who are most likely to benefit from this therapy...
August 3, 2017: Diabetologia
https://www.readbyqxmd.com/read/28770328/metformin-and-ageing-improving-ageing-outcomes-beyond-glycaemic-control
#18
REVIEW
Willy Marcos Valencia, Ana Palacio, Leonardo Tamariz, Hermes Florez
In a world where the population is ageing, there is growing interest and demand for research evaluating strategies that address the ageing process. After 60 years of successful use of metformin in our pharmaceutical armamentarium, we are learning that, beyond improving glycaemic control, metformin may have additional mechanisms and pathways of action that need further study. Although, metformin's effect on clinical ageing outcomes may still be considered speculative, the findings from studies into cellular and animal models and from observational and pilot human studies support the existence of beneficial effects on ageing...
August 2, 2017: Diabetologia
https://www.readbyqxmd.com/read/28770321/metformin-clinical-use-in-type-2-diabetes
#19
REVIEW
Elizabeth Sanchez-Rangel, Silvio E Inzucchi
Metformin is one of the most popular oral glucose-lowering medications, widely considered to be the optimal initial therapy for patients with type 2 diabetes mellitus. Interestingly, there still remains controversy regarding the drug's precise mechanism of action, which is thought to involve a reduction in hepatic glucose production. It is now recommended as first-line treatment in various guidelines, including that of the EASD and ADA. Its favoured status lies in its efficacy, low cost, weight neutrality and good safety profile...
August 2, 2017: Diabetologia
https://www.readbyqxmd.com/read/28769124/metformin-inhibits-cyst-formation-in-a-zebrafish-model-of-polycystin-2-deficiency
#20
Ming-Yang Chang, Tsu-Lin Ma, Cheng-Chieh Hung, Ya-Chung Tian, Yung-Chang Chen, Chih-Wei Yang, Yi-Chuan Cheng
Autosomal dominant polycystic kidney disease (ADPKD) is a common kidney disease caused by mutations in PKD1 or PKD2. Metformin reduces cyst growth in mouse models of PKD1. However, metformin has not been studied in animal models of PKD2, and the cellular mechanism underlying its effectiveness is not entirely clear. This study investigated the effects of metformin on cyst formation in a zebrafish model of polycystin-2 deficiency resulting from morpholino knockdown of pkd2. We added metformin (2.5 to 20 mM) to the embryo media between 4 and 48 hours post fertilisation and observed pronephric cyst formation by using the wt1b promoter-driven GFP signal in Tg(wt1b:GFP) pkd2 morphants...
August 2, 2017: Scientific Reports
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