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https://www.readbyqxmd.com/read/28646699/insulin-and-the-polycystic-ovary-syndrome
#1
REVIEW
Djuro Macut, Jelica Bjekić-Macut, Dario Rahelić, Mirjana Doknić
Polycystic ovary syndrome (PCOS) is the most prevalent endocrinopathy among women during reproductive age. PCOS is characterised by hyperandrogenaemia, hyperinsulinaemia, and deranged adipokines secretion from the adipose tissue. In addition to the reduced insulin sensitivity, PCOS women exhibit β-cell dysfunction as well. Low birth weight and foetal exposure to androgens may contribute to the development of the PCOS phenotype during life. Further metabolic complications lead to dyslipidaemia, worsening obesity and glucose tolerance, high prevalence of metabolic syndrome, and greater susceptibility to diabetes...
June 12, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28644886/complex-i-inhibition-augments-dichloroacetate-cytotoxicity-through-enhancing-oxidative-stress-in-vm-m3-glioblastoma-cells
#2
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
#3
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/28641684/novel-indications-for-commonly-used-medications-as-radiation-protectants-in-spaceflight
#4
Mark F McLaughlin, Dorit B Donoviel, Jeffrey A Jones
In the space environment, the traditional radioprotective principles of time, distance, and shielding become difficult to implement. Additionally, the complex radiation environment inherent in space, the chronic exposure timeframe, and the presence of numerous confounding variables complicate the process of creating appropriate risk models for astronaut exposure. Pharmaceutical options hold tremendous promise to attenuate acute and late effects of radiation exposure in the astronaut population. Pharmaceuticals currently approved for other indications may also offer radiation protection, modulation, or mitigation properties along with a well-established safety profile...
July 1, 2017: Aerospace Medicine and Human Performance
https://www.readbyqxmd.com/read/28641310/potentiating-the-effects-of-radiotherapy-in-rectal-cancer-the-role-of-aspirin-statins-and-metformin-as-adjuncts-to-therapy
#5
K J Gash, A C Chambers, D E Cotton, A C Williams, M G Thomas
BACKGROUND: Complete tumour response (pCR) to neo-adjuvant chemo-radiotherapy for rectal cancer is associated with a reduction in local recurrence and improved disease-free and overall survival, but is achieved in only 20-30% of patients. Drug repurposing for anti-cancer treatments is gaining momentum, but the potential of such drugs as adjuncts, to increase tumour response to chemo-radiotherapy in rectal cancer, is only just beginning to be recognised. METHODS: A systematic literature search was conducted and all studies investigating the use of drugs to enhance response to neo-adjuvant radiation in rectal cancer were included...
June 22, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28640441/adipose-tissue-derived-omentin-1-function-and-regulation
#6
Takuya Watanabe, Kaho Watanabe-Kominato, Yui Takahashi, Miho Kojima, Rena Watanabe
Omentin-1, also known as intelectin-1, is a recently identified novel adipocytokine of 313 amino acids, which is expressed in visceral (omental and epicardial) fat as well as mesothelial cells, vascular cells, airway goblet cells, small intestine, colon, ovary, and plasma. The level of omentin-1 expression in (pre)adipocytes is decreased by glucose/insulin and stimulated by fibroblast growth factor-21 and dexamethasone. Several lines of experimental evidence have shown that omentin-1 plays crucial roles in the maintenance of body metabolism and insulin sensitivity, and has anti-inflammatory, anti-atherosclerotic, and cardiovascular protective effects via AMP-activated protein kinase/Akt/nuclear factor-κB/mitogen-activated protein kinase (ERK, JNK, and p38) signaling...
June 18, 2017: Comprehensive Physiology
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
#7
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/28632474/evaluation-of-the-concurrent-use-of-dolutegravir-and-metformin-in-human-immunodeficiency-virus-infected-patients
#8
Anne Masich, Melissa E Badowski, Michelle D Liedtke, Patricia P Fulco
An analysis of the interaction between dolutegravir and metformin was conducted in the HIV ambulatory clinic setting. This was a multicenter, retrospective case series evaluating adult, HIV-infected patients concurrently prescribed dolutegravir and metformin. Historical electronic medical records were utilized to collect case-specific data. Laboratory parameters including serum creatinine (SCr), hemoglobin A1c (HgbA1c), plasma HIV RNA, CD4 cell count, and lactate were reviewed. Adverse drug reactions were assessed using patient-reported gastrointestinal intolerance and hypoglycemic symptoms...
January 1, 2017: International Journal of STD & AIDS
https://www.readbyqxmd.com/read/28631762/-safety-and-tolerability-of-oral-hypoglycemic-therapies-in-type-2-diabetes-mellitus-patients-at-high-cardiovascular-risk
#9
Giuseppe Ambrosio, Gaetano M De Ferrari, Massimo Federici, Pasquale Perrone Filardi
Oral hypoglycemic drugs for type 2 diabetes aim at preventing the metabolic effects of hyperglycemia and cardiovascular (CV) events. The evidence of the possible CV risk related to the prescription of some antidiabetic drugs prompted regulatory agencies to require safety studies. This review provides an updated analysis of CV safety profiles for antidiabetic drugs used for the treatment of patients with high CV risk.The most recent studies analyze different aspects of CV morbidity, such as ischemic events, heart failure and arrhythmia, and their interactions with hyperglycemia...
June 2017: Giornale Italiano di Cardiologia
https://www.readbyqxmd.com/read/28628926/synthesis-characterisation-molecular-docking-anti-microbial-and-anti-diabetic-screening-of-substituted-4-indolylphenyl-6-arylpyrimidine-2-imine-derivatives
#10
Veerasamy Ramya, Santhirakasu Vembu, Ganesan Ariharasivakumar, Manathusamy Gopalakrishnan
The purpose of the research is to synthesise a novel series of (E)-2-(4-(1H-indol-3-yl)-6-p-substituted phenylpyrimidin-2-yl)dimethylguanidine derivatives since 3-(1H-indol-3-yl)-1-p-substituted phenylprop-2-en-1-one and evaluate their molecular docking studies, antimicrobial, and anti-diabetic activities. Among all the synthesized compounds (11a-g), compound 11a exhibits excellent CDOCKER energy (-11.36 kcal/mol). The entire compounds (11a-g) confirm very good antimicrobial activity towards the tested microorganisms...
June 19, 2017: Drug Research
https://www.readbyqxmd.com/read/28621668/blocking-epithelial-to-mesenchymal-transition-in-glioblastoma-with-a-sextet-of-repurposed-drugs-the-eis-regimen
#11
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
#12
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/28619830/differential-and-joint-effects-of-metformin-and-statins-on-overall-survival-of-elderly-patients-with-pancreatic-adenocarcinoma-a-large-population-based-study
#13
Jian-Yu E, Shou-En Lu, Yong Lin, Judith M Graber, David Rotter, Lanjing Zhang, Gloria M Petersen, Kitaw Demissie, Grace Lu-Yao, Xiang-Lin Tan
BACKGROUND: Published evidence indicates that individual use of metformin and statin is associated with reduced cancer mortality. However, their differential and joint effects on pancreatic cancer survival are inconclusive. METHODS: We identified a large population-based cohort of 12,572 patients aged 65 years or older with primary pancreatic ductal adenocarcinoma (PDAC) diagnosed between 2008 and 2011 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database...
June 15, 2017: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/28618992/modulating-mitophagy-in-mitochondrial-disease
#14
Eszter Dombi, Heather Mortiboys, Joanna Poulton
Mitochondrial diseases may result from mutations in the maternally-inherited mitochondrial DNA (mtDNA) or from mutations in nuclear genes encoding mitochondrial proteins. Their bi-genomic nature makes mitochondrial diseases a very heterogeneous group of disorders that can present at any age and can affect any type of tissue. The autophagic-lysosomal degradation pathway plays an important role in clearing dysfunctional and redundant mitochondria through a specific quality control mechanism termed mitophagy. Mitochondria could be targeted for autophagic degradation for a variety of reasons including basal turnover for recycling, starvation induced degradation, and degradation due to damage...
June 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28618017/curcumin-and-metformin-mediated-chemoprevention-of-oral-cancer-is-associated-with-inhibition-of-cancer-stem-cells
#15
Gangotri Siddappa, Safeena Kulsum, Doddathimmasandra Ramanjanappa Ravindra, Vinay V Kumar, Nalini Raju, Nisheena Raghavan, Holalugunda Vittalamurthy Sudheendra, Anupam Sharma, Sumsum P Sunny, Tina Jacob, Binu T Kuruvilla, Merina Benny, Benny Antony, Mukund Seshadri, Padma Lakshminarayan, Wesley Hicks, Amritha Suresh, Moni A Kuriakose
Effective chemoprevention is critical for improving outcomes of oral cancer. As single agents, curcumin and metformin, are reported to exhibit chemopreventive properties, in vitro as well as in patients with oral cancer. In this study, the chemopreventive efficacy of this drug combination was tested in a 4NQO (4-nitro-quinoline-oxide) induced, mice oral carcinogenesis model. Molecular analysis revealed a cancer stem cell (CSC)-driven, oral carcinogenic progression in this model, wherein a progressive increase in the expression of CSC-specific markers (CD44 and CD133) was observed from 8th to 25th week, at transcript (40 to 100 fold) and protein levels (p≤0...
June 15, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28616837/a-phase-ib-study-of-everolimus-combined-with-metformin-for-patients-with-advanced-cancer
#16
Remco J Molenaar, Tim van de Venne, Mariëtte J Weterman, Ron A Mathot, Heinz-Josef Klümpen, Dick J Richel, Johanna W Wilmink
Background The efficacy to monotherapy with the mTOR inhibitor everolimus in advanced cancer is often limited due to therapy resistance. Combining everolimus with metformin may decrease the chance of therapy resistance. Methods Patients received everolimus and metformin in a 3 + 3 dose-escalation scheme. Objectives were to determine the dose-limiting toxicities (DLTs), maximum tolerated dose, toxic effects, pharmacokinetics and anti-tumour efficacy. Results 9 patients received study treatment for a median duration of 48 days (range: 4-78)...
June 15, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28616207/changes-in-metformin-use-in-chronic-kidney-disease
#17
Talha H Imam
Metformin is one of the oldest and most widely prescribed antidiabetic medicines worldwide. It is the only such medicine that has shown a reduction of cardiovascular mortality in diabetes mellitus type 2. Since many diabetic patients have chronic kidney disease, its use is often curtailed by practitioners due to fear of lactic acidosis and the US Food and Drug Administration (FDA) warnings that, until recently, had been in place for decades. Current guidelines, though somewhat vague regarding dosages, clearly pave the way for spreading the use of metformin in patients with lower glomerular filtration rates...
June 2017: Clinical Kidney Journal
https://www.readbyqxmd.com/read/28615356/sulforaphane-reduces-hepatic-glucose-production-and-improves-glucose-control-in-patients-with-type-2-diabetes
#18
Annika S Axelsson, Emily Tubbs, Brig Mecham, Shaji Chacko, Hannah A Nenonen, Yunzhao Tang, Jed W Fahey, Jonathan M J Derry, Claes B Wollheim, Nils Wierup, Morey W Haymond, Stephen H Friend, Hindrik Mulder, Anders H Rosengren
A potentially useful approach for drug discovery is to connect gene expression profiles of disease-affected tissues ("disease signatures") to drug signatures, but it remains to be shown whether it can be used to identify clinically relevant treatment options. We analyzed coexpression networks and genetic data to identify a disease signature for type 2 diabetes in liver tissue. By interrogating a library of 3800 drug signatures, we identified sulforaphane as a compound that may reverse the disease signature...
June 14, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28615288/correlation-between-apparent-substrate-affinity-and-oct2-transporter-turnover
#19
Alyscia Cory Severance, Philip J Sandoval, Stephen H Wright
Organic cation transporter 2 (OCT2) mediates the first step in the renal secretion of many cationic drugs: basolateral uptake from blood into proximal tubule cells. The impact of this process on the pharmacokinetics of drug clearance as estimated using a physiologically-based pharmacokinetic (PBPK) approach relies on an accurate understanding of the kinetics of transport because the ratio of the maximal rate of transport to the Michaelis constant (i.e., Jmax/Kt) provides an estimate of the intrinsic clearance (Clint) used in in vitro-in vivo extrapolation of experimentally determined transport data...
June 14, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28614117/role-of-amp-activated-protein-kinase-in-kidney-tubular-transport-metabolism-and-disease
#20
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
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