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https://www.readbyqxmd.com/read/28541801/enemies-or-weapons-in-hands-investigational-anti-diabetic-drug-glibenclamide-and-cancer-risk
#1
Rui Gao, Tao Yang, Wei Xu
Epidemiological evidence suggests that diabetes is associated with elevated cancer risk through the actions of hyperglycemia, hyperinsulinemia and chronic inflammation. Metformin, a first-line medication for type 2 diabetes mellitus, arouses growing concerns on its anti-cancer effect. However, data regarding the effect of glibenclamide on tumor growth and cancer risk are less consistent, which may be a potential anti-cancer drug. Areas covered: In this review, we clarified probable underlying mechanisms in preclinical studies and reviewed epidemiological evidence on glibenclamide's cancer risk in clinical studies...
May 25, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28538088/effects-of-the-insulin-sensitizer-metformin-in-alzheimer-disease-pilot-data-from-a-randomized-placebo-controlled-crossover-study
#2
Aaron M Koenig, Dawn Mechanic-Hamilton, Sharon X Xie, Martha F Combs, Anne R Cappola, Long Xie, John A Detre, David A Wolk, Steven E Arnold
Epidemiological studies have identified a robust association between type II diabetes mellitus and Alzheimer disease (AD), and neurobiological studies have suggested the presence of central nervous system insulin resistance in individuals with AD. Given this association, we hypothesized that the central nervous system-penetrant insulin-sensitizing medication metformin would be beneficial as a disease-modifying and/or symptomatic therapy for AD, and conducted a placebo-controlled crossover study of its effects on cerebrospinal fluid (CSF), neuroimaging, and cognitive biomarkers...
April 2017: Alzheimer Disease and Associated Disorders
https://www.readbyqxmd.com/read/28530702/metformin-alters-the-gut-microbiome-of-individuals-with-treatment-naive-type-2-diabetes-contributing-to-the-therapeutic-effects-of-the-drug
#3
Hao Wu, Eduardo Esteve, Valentina Tremaroli, Muhammad Tanweer Khan, Robert Caesar, Louise Mannerås-Holm, Marcus Ståhlman, Lisa M Olsson, Matteo Serino, Mercè Planas-Fèlix, Gemma Xifra, Josep M Mercader, David Torrents, Rémy Burcelin, Wifredo Ricart, Rosie Perkins, José Manuel Fernàndez-Real, Fredrik Bäckhed
Metformin is widely used in the treatment of type 2 diabetes (T2D), but its mechanism of action is poorly defined. Recent evidence implicates the gut microbiota as a site of metformin action. In a double-blind study, we randomized individuals with treatment-naive T2D to placebo or metformin for 4 months and showed that metformin had strong effects on the gut microbiome. These results were verified in a subset of the placebo group that switched to metformin 6 months after the start of the trial. Transfer of fecal samples (obtained before and 4 months after treatment) from metformin-treated donors to germ-free mice showed that glucose tolerance was improved in mice that received metformin-altered microbiota...
May 22, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28530382/diabetes-update-new-pharmacotherapy-for-type-2-diabetes
#4
Beth Choby
Multiple new drugs for managing type 2 diabetes have entered the market in the past 5 years. Guidelines from the American Diabetes Association recommend metformin for initial therapy, followed by a second drug if A1c goals are not met or initially for patients with A1c levels greater than 9%. Conversely, the American Association of Clinical Endocrinologists recommends initial management with two drugs if the A1c level is greater than 7.5%. The risk of lactic acidosis associated with metformin has been shown to be less than previously thought, with newer guidelines permitting use with an estimated glomerular filtration rate of 45 to 60 mL/min/1...
May 2017: FP Essentials
https://www.readbyqxmd.com/read/28529619/effects-of-prolonged-exposure-to-low-dose-metformin-in-thyroid-cancer-cell-lines
#5
Safar Kheder, Karen Sisley, Sirwan Hadad, Sabapathy P Balasubramanian
Background: Thyroid cancer is generally associated with an excellent prognosis, but there is significant long-term morbidity with standard treatment. Some sub-types however have a poor prognosis. Metformin, an oral anti-diabetic drug is shown to have anti-cancer effects in several types of cancer (breast, lung and ovarian cancer). The proposed mechanisms include activation of the Adenosine Mono-phosphate-activated Protein Kinase (AMPK) pathway and inhibition of the mTOR pathway (which promotes growth and proliferation)...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28529553/progress-in-the-application-and-mechanism-of-metformin-in-treating-non-small-cell-lung-cancer
#6
Chan Li, Yang Xue, Yu-Rong Xi, Ke Xie
At present, the incidence and mortality of lung cancer demonstrate an increasing trend. Non-small cell lung cancer (NSCLC) accounts for ~80-85% of all lung cancer cases. Therefore, developing novel and more effective treatments is of great importance. The use of combination therapies, where several anticancer agents are used together, is a promising strategy. Recent studies demonstrate that metformin, which has been utilized for treating diabetes mellitus for >50 years, has antitumor effects in numerous types of cancer including NSCLC...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28529539/jiangtang-decoction-ameliorate-diabetic-nephropathy-through-the-regulation-of-pi3k-akt-mediated-nf-%C3%AE%C2%BAb-pathways-in-kk-ay-mice
#7
Jin-Ni Hong, Wei-Wei Li, Lin-Lin Wang, Hao Guo, Yong Jiang, Yun-Jia Gao, Peng-Fei Tu, Xue-Mei Wang
BACKGROUND: Jiangtang decoction (JTD) is a China patented drug which contains Euphorbia humifusa Willd, Salvia miltiorrhiza Bunge, Astragalus mongholicus Bunge, Anemarrhena asphodeloides Bunge, and Coptis chinensis Franch. For decades, it has also been used clinically to treat diabetic nephropathy (DN) effectively; however, the associated mechanisms remain unknown. Thus, the present study aimed to examine the protective efficacy of JTD in DN and elucidate the underlying molecular mechanisms...
2017: Chinese Medicine
https://www.readbyqxmd.com/read/28526827/activated-hepatic-stellate-cells-secrete-periostin-to-induce-stem-cell-like-phenotype-of-residual-hepatocellular-carcinoma-cells-after-heat-treatment
#8
Rui Zhang, Rong-Rong Yao, Jing-Huan Li, Gang Dong, Min Ma, Qiong-Dan Zheng, Dong-Mei Gao, Jie-Feng Cui, Zheng-Gang Ren, Rong-Xin Chen
Some evidences show that residual tumor after thermal ablation will progress rapidly. However, its mechanisms remain unclear. Here, we assessed whether activated HSCs could regulate stem cell-like property of residual tumor after incomplete thermal ablation to promote tumor progression. Human HCC cell lines were exposed to sublethal heat treatment to simulate the peripheral zone of thermal ablation. After residual HCC cells were cultured with conditional medium (CM) from activated HSCs, parameters of the stem cell-like phenotypes were analyzed...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28522373/population-pharmacokinetics-of-carvedilol-enantiomers-and-their-metabolites-in-type-2-diabetes-and-healthy-subjects
#9
Glauco H B Nardotto, Vera L Lanchote, Eduardo B Coelho, Oscar Della Pasqua
Carvedilol, a drug available as a racemic mixture, is eliminated as hydroxyphenylcarvedilol (OHC) by CYP2D6 and O-desmethylcarvedilol (DMC) by CYP2C9 followed by conjugation to glucuronides. In contrast to other β-adrenergic receptor antagonists, carvedilol does not induce insulin resistance or worsen glycaemic control in the diabetic hypertensive patients. This study aims to investigate the implications of type 2 diabetes (T2DM) on the pharmacokinetics of carvedilol enantiomers using an integrated population pharmacokinetic modelling approach...
May 15, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28521682/repurposing-of-copper-ii-chelating-drugs-for-the-treatment-of-neurodegenerative-diseases
#10
Valeria Lanza, Danilo Milardi, Giuseppe Di Natale, Giuseppe Pappalardo
BACKGROUND: There is mounting urgency to find new drugs for the treatment of neurodegenerative disorders. A large number of reviews has exhaustively described either the molecular or clinical aspects of neurodegenerative diseases as Alzheimer's (AD) and Parkinson's (PD). Conversely, reports outlining how known drugs in use for other diseases can be also effective as therapeutic agents in neurodegenerative diseases are less reported. This review focuses on the current uses of some copper(II) interacting molecules as potential drug candidates in neurodegeneration...
May 17, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28507773/rapid-onset-clozapine-induced-loss-of-glycaemic-control-case-report
#11
Alejandro Porras-Segovia, Amir Krivoy, Mark Horowitz, George Thomas, Mark Bolstridge, Dragos Ion, Sukhwinder S Shergill
Clozapine has proved to be an effective antipsychotic for the treatment of refractory schizophrenia - characterised by the persistence of symptoms despite optimal treatment trials with at least two different antipsychotics at adequate dose and duration - but its use is hampered by adverse effects. The development of clozapine-induced diabetes is commonly considered to arise as part of a metabolic syndrome, associated with weight gain, and thus evolves slowly. We present the case of an individual with refractory schizophrenia and metformin-controlled diabetes who developed rapid-onset insulin-dependent hyperglycaemia immediately after starting clozapine...
May 2017: BJPsych Open
https://www.readbyqxmd.com/read/28502303/-effect-of-metformin-on-proliferation-and-apoptosis-of-rat-prolactinoma-mmq-cells-and-related-mechanisms
#12
Kai Jin, Lunliang Ruan, Jiujun Pu, Ailing Zhong, Fuchao Wang, Song Tan, Hua Huang, Jiamin Mou, Gang Yang
Objective To investigate the effect of metformin on the cell proliferation, cell cycle and apoptosis of rat prolactinoma MMQ cells in vitro and related molecular mechanisms. Methods The MMQ cells were treated with 1.25, 2.5, 5, 10, 20 mmol/L metformin for 48 hours. CCK-8 assay was used to assess the cell proliferation ability; flow cytometry was used to analyze the cell cycle distribution and apoptosis; Western blotting was performed to detect the expressions of AMPKα1/2, p-AMPKα, mTOR, p-mTOR, insulin like growth factor 1 receptor (IGF-1R), ERK1/2, p-ERK1/2, AKT, p-AKT, P21, CDK4, cyclin D1, caspase-3, cleaved caspase-3(c-caspase-3), Bcl-2 and BAX...
May 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28499942/metformin-ameliorates-hypoxia-reoxygenation-induced-cardiomyocyte-apoptosis-based-on-the-sirt3-signaling-pathway
#13
Yanyan Du, Jingjing Zhang, Fang Fang, Xiqing Wei, Hongsheng Zhang, Hongyong Tan, Jinguo Zhang
Myocardial hypoxia/reoxygenation (H/R) injury is one of the main causes of death and disability worldwide. However, a limited number of therapies are available to minimize the detrimental effects of this injury. Recently, researchers have demonstrated that metformin exerts direct cardioprotective effects against H/R. The aim of this study was to investigate the underlying mechanisms of how metformin affects myocardial hypoxia/reoxygenation (H/R) injury. In our study, the activities of lactate dehydrogenase (LDH) and superoxide dismutase (SOD) as well as the levels of malondialdehyde (MDA) were measured...
May 9, 2017: Gene
https://www.readbyqxmd.com/read/28498475/targeting-hexokinase-2-inhibition-promotes-radiosensitization-in-hpv16%C3%A2-e7-induced-cervical-cancer-and-suppresses-tumor-growth
#14
Yuan Liu, Tracy Murray-Stewart, Robert A Casero, Ioannis Kagiampakis, Lihua Jin, Jiawen Zhang, Huihui Wang, Qi Che, Huan Tong, Jieqi Ke, Feizhou Jiang, Fangyuan Wang, Xiaoping Wan
In order to improve the sensitivity of cervical cancer cells to irradiation therapy, we targeted hexokinase 2 (HK2), the first rate-limiting enzyme of glycolysis, and explore its role in cervical cancer cells. We suppressed HK2 expression and/or function by shRNA and/or metformin and found HK2 inhibition enhanced cells apoptosis with accelerating expression of cleaved PARP and caspase-3. HK2 inhibition also induced much inferior proliferation of cervical cancer cells both in vitro and in vivo with diminishing expression of mTOR, MIB and MGMT...
June 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28497164/metformin-prevents-ischaemic-ventricular-fibrillation-in-metabolically-normal-pigs
#15
Li Lu, Shuyu Ye, Rebecca L Scalzo, Jane E B Reusch, Clifford R Greyson, Gregory G Schwartz
AIMS/HYPOTHESIS: Metformin is the drug most often used to treat type 2 diabetes. Evidence suggests that metformin may reduce mortality of individuals with type 2 diabetes, but the mechanism of such an effect is unknown and outcomes of metformin treatment in people without diabetes have not been determined. If metformin favourably affected mortality of non-diabetic individuals, it might have even broader therapeutic utility. We evaluated the effect of metformin on myocardial energetics and ischaemic ventricular fibrillation (VF) in metabolically normal pigs...
May 11, 2017: Diabetologia
https://www.readbyqxmd.com/read/28480051/metformin-suppresses-triple-negative-breast-cancer-stem-cells-by-targeting-klf5-for-degradation
#16
Peiguo Shi, Wenjing Liu, Tala, Haixia Wang, Fubing Li, Hailin Zhang, Yingying Wu, Yanjie Kong, Zhongmei Zhou, Chunyan Wang, Wenlin Chen, Rong Liu, Ceshi Chen
Out of the breast cancer subtypes, triple-negative breast cancer (TNBC) has the poorest prognosis without effective targeted therapies. Metformin, a first-line drug for type 2 diabetes mellitus, was demonstrated to target breast cancer stem cells selectively. However, the efficiency and the mechanism of action of metformin in TNBC are unclear. In this study, we demonstrated that metformin decreased the percentage of TNBC stem cells partially through the downregulation of the expression of the stem cell transcription factor Krüppel-like factor 5 (KLF5) and its downstream target genes, such as Nanog and FGF-BP1, in TNBC cell lines...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28471233/effect-of-sodium-aescinate-treatment-on-pcos-rat-model-with-insulin-resistance
#17
L Chen, L M Hu, Y F Wang, H Y Yang, X Y Huang, W Zhou, H X Sun
BACKGROUND: Recent studies indicated that insulin resistance may contribute to the pathogenesis of polycystic ovary syndrome (PCOS); however, the specific mechanism is still unclear. OBJECTIVE: To investigate the effect of sodium aescinate (SA) on PCOS-IR rat models. METHODS: Sixty rats were randomly divided into the five groups: un-treated rats (n = 12), PCOS-IR group (n = 12), PCOS-IR group plus 50 mg/kg SA (n = 12), PCOS-IR group plus 10 mg/kg SA (n = 12), PCOS-IR group plus 150 mg/kg metformin (n = 12)...
2017: Bratislavské Lekárske Listy
https://www.readbyqxmd.com/read/28465536/metformin-disrupts-malignant-behavior-of-oral-squamous-cell-carcinoma-via-a-novel-signaling-involving-late-sv40-factor-aurora-a
#18
Chang-Han Chen, Hsin-Ting Tsai, Hui-Ching Chuang, Li-Yen Shiu, Li-Jen Su, Tai-Jan Chiu, Sheng-Dean Luo, Fu-Min Fang, Chao-Cheng Huang, Chih-Yen Chien
Conventional therapeutic processes in patient with OSCC are associated with several unfavorable effects leading to patients with poor survival rate. Metformin has been shown to protect against a variety of specific diseases, including cancer. However, the precise roles and mechanisms underlying the therapeutic effects of metformin on OSCC remain elusive. In the current study, in vitro and xenograft model experiments revealed that metformin inhibited growth and metastasis of oral cancer cells. Importantly, metformin-restrained tumorigenesis of oral cancer was accompanied with strong decrease of both Aurora-A and Late SV40 Factor (LSF) expressions...
May 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28464864/metformin-produces-growth-inhibitory-effects-in-combination-with-nutlin-3a-on-malignant-mesothelioma-through-a-cross-talk-between-mtor-and-p53-pathways
#19
Kengo Shimazu, Yuji Tada, Takao Morinaga, Masato Shingyoji, Ikuo Sekine, Hideaki Shimada, Kenzo Hiroshima, Takao Namiki, Koichiro Tatsumi, Masatoshi Tagawa
BACKGROUND: Mesothelioma is resistant to conventional treatments and is often defective in p53 pathways. We then examined anti-tumor effects of metformin, an agent for type 2 diabetes, and combinatory effects of metformin and nutlin-3a, an inhibitor for ubiquitin-mediated p53 degradation, on human mesothelioma. METHODS: We examined the effects with a colorimetric assay and cell cycle analyses, and investigated molecular events in cells treated with metformin and/or nutlin-3a with Western blot analyses...
May 2, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28464031/18f-fdg-uptake-in-the-colon-is-modulated-by-metformin-but-not-associated-with-core-body-temperature-and-energy-expenditure
#20
Lonneke Bahler, Frits Holleman, Man-Wai Chan, Jan Booij, Joost B Hoekstra, Hein J Verberne
PURPOSE: Physiological colonic 18F-fluorodeoxyglucose (18F-FDG) uptake is a frequent finding on 18F-FDG positron emission tomography computed tomography (PET-CT). Interestingly, metformin, a glucose lowering drug associated with moderate weight loss, is also associated with an increased colonic 18F-FDG uptake. Consequently, increased colonic glucose use might partly explain the weight losing effect of metformin when this results in an increased energy expenditure and/or core body temperature...
2017: PloS One
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