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https://www.readbyqxmd.com/read/28926637/selective-cytotoxicity-of-the-anti-diabetic-drug-metformin-in-glucose-deprived-chicken-dt40-cells
#1
Kei Kadoda, Takahito Moriwaki, Masataka Tsuda, Hiroyuki Sasanuma, Masamichi Ishiai, Minoru Takata, Hiroshi Ide, Shin-Ichiro Masunaga, Shunichi Takeda, Keizo Tano
Metformin is a biguanide drug that is widely used in the treatment of diabetes. Epidemiological studies have indicated that metformin exhibits anti-cancer activity. However, the molecular mechanisms underlying this activity currently remain unclear. We hypothesized that metformin is cytotoxic in a tumor-specific environment such as glucose deprivation and/or low oxygen (O2) tension. We herein demonstrated that metformin was highly cytotoxic under glucose-depleted, but not hypoxic (2% O2) conditions. In order to elucidate the underlying mechanisms of this selective cytotoxicity, we treated exposed DNA repair-deficient chicken DT40 cells with metformin under glucose-depleted conditions and measured cellular sensitivity...
2017: PloS One
https://www.readbyqxmd.com/read/28923861/mct1-inhibitor-azd3965-increases-mitochondrial-metabolism-facilitating-combination-therapy-and-non-invasive-magnetic-resonance-spectroscopy
#2
Mounia Beloueche-Babari, Slawomir Wantuch, Teresa Casals Galobart, Markela Koniordou, Harold G Parkes, Vaitha Arunan, Yuen-Li Chung, Thomas R Eykyn, Paul D Smith, Martin O Leach
Monocarboxylate transporters (MCT) modulate tumor cell metabolism and offer promising therapeutic targets for cancer treatment. Understanding the impact of MCT blockade on tumor cell metabolism may help develop combination strategies or identify pharmacodynamic biomarkers to support the clinical development of MCT inhibitors now in clinical trials. In this study, we assessed the impact of the MCT1 inhibitor AZD3965 on cancer cell metabolism in vitro and in vivo. Exposing human lymphoma and colon carcinoma cells to AZD3965 increased MCT4-dependent accumulation of intracellular lactate, inhibiting monocarboxylate influx and efflux...
September 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28923291/use-of-prohibited-medication-a-potentially-overlooked-confounder-in-clinical-trials-omarigliptin-once-weekly-dpp-4-inhibitor-monotherapy-trial-in-18-to-45-year-olds
#3
Ira Gantz, Liubov Sokolova, Lokesh Jain, Carol Iredale, Edward A O'Neill, Ziwen Wei, Raymond Lam, Shailaja Suryawanshi, Keith D Kaufman, Samuel S Engel, Eseng Lai
PURPOSE: The objective of this clinical trial was to assess the efficacy and safety of omarigliptin monotherapy in young adult patients with type 2 diabetes mellitus (T2DM). Unexpected efficacy results in this trial led to a series of investigations that identified the use of prohibited medication by a substantial number of trial patients. METHODS: Patients with T2DM who were ≥18 to <45 years of age and either drug-naive or not on an antihyperglycemic agent for ≥12 weeks with inadequate glycemic control were randomized in a double-blind manner to receive omarigliptin 25 mg once weekly (n = 102) or placebo once weekly (n = 101) for 24 weeks...
September 15, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28922161/comorbidity-analysis-between-alzheimer-s-disease-and-type-2-diabetes-mellitus-t2dm-based-on-shared-pathways-and-the-role-of-t2dm-drugs
#4
Reagon Karki, Alpha Tom Kodamullil, Martin Hofmann-Apitius
BACKGROUND: Various studies suggest a comorbid association between Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) indicating that there could be shared underlying pathophysiological mechanisms. OBJECTIVE: This study aims to systematically model relevant knowledge at the molecular level to find a mechanistic rationale explaining the existing comorbid association between AD and T2DM. METHOD: We have used a knowledge-based modeling approach to build two network models for AD and T2DM using Biological Expression Language (BEL), which is capable of capturing and representing causal and correlative relationships at both molecular and clinical levels from various knowledge resources...
September 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28921919/oral-glucose-lowering-with-linagliptin-and-metformin-compared-with-linagliptin-alone-as-initial-treatment-in-asian-patients-with-newly-diagnosed-type-2-diabetes-and-marked-hyperglycemia-subgroup-analysis-of-a-randomized-clinical-trial
#5
Ronald Cw Ma, Stefano Del Prato, Baptist Gallwitz, Vyankatesh K Shivane, Diane Lewis-D'Agostino, Zelie Bailes, Sanjay Patel, Jisoo Lee, Maximilian von Eynatten, Maximiliano Di Domenico, Stuart A Ross
AIMS/INTRODUCTION: Type 2 diabetes mellitus (T2DM) is an epidemic in Asia, yet clinical trials of glucose-lowering therapies often enrol predominantly Western populations. We explored the initial combination of metformin and linagliptin, a dipeptidyl peptidase-4 inhibitor, in newly diagnosed T2DM patients in Asia with marked hyperglycemia. MATERIALS AND METHODS: This was a post-hoc subgroup analysis of a multinational, parallel-group clinical trial in which 316 newly diagnosed T2DM patients with glycated hemoglobin A1c (HbA1c) 8...
September 16, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28919040/heme-binding-biguanides-target-cytochrome-p450-dependent-cancer-cell-mitochondria
#6
Zhijun Guo, Irina F Sevrioukova, Ilia G Denisov, Xia Zhang, Ting-Lan Chiu, Dafydd G Thomas, Eric A Hanse, Rebecca A D Cuellar, Yelena V Grinkova, Vanessa Wankhede Langenfeld, Daniel S Swedien, Justin D Stamschror, Juan Alvarez, Fernando Luna, Adela Galván, Young Kyung Bae, Julia D Wulfkuhle, Rosa I Gallagher, Emanuel F Petricoin, Beverly Norris, Craig M Flory, Robert J Schumacher, M Gerard O'Sullivan, Qing Cao, Haitao Chu, John D Lipscomb, William M Atkins, Kalpna Gupta, Ameeta Kelekar, Ian A Blair, Jorge H Capdevila, John R Falck, Stephen G Sligar, Thomas L Poulos, Gunda I Georg, Elizabeth Ambrose, David A Potter
The mechanisms by which cancer cell-intrinsic CYP monooxygenases promote tumor progression are largely unknown. CYP3A4 was unexpectedly associated with breast cancer mitochondria and synthesized arachidonic acid (AA)-derived epoxyeicosatrienoic acids (EETs), which promoted the electron transport chain/respiration and inhibited AMPKα. CYP3A4 knockdown activated AMPKα, promoted autophagy, and prevented mammary tumor formation. The diabetes drug metformin inhibited CYP3A4-mediated EET biosynthesis and depleted cancer cell-intrinsic EETs...
August 29, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28918830/metformin-has-positive-therapeutic-effects-in-colon-cancer-and-lung-cancer
#7
DeAnna Henderson, Danielle Frieson, Jeffrey Zuber, Solomon S Solomon
BACKGROUND: Metformin (MF), a diabetic drug, has antineoplastic activity as adjuvant therapy for breast cancer and prostate cancer. MF is thought to work via inhibition of mammalian target of rapamycin and activation of p53 and liver kinase B1 via adenosine 5'-monophosphate-activated protein kinase. We investigated survival, recurrences and metastasis in patients with type 2 diabetes mellitus (DM2) along with colorectal cancer (CC) or lung cancer (LC) taking MF using the electronic medical record in Memphis Veterans Affairs Medical Center (colon, n = 202; lung, n = 180)...
September 2017: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/28915221/metformin-exerts-beneficial-effects-in-hemorrhagic-shock-in-an-ampk%C3%AE-1-independent-manner
#8
Paul Kim, Giovanna Piraino, Michael O'Connor, Paul W Hake, Vivian Wolfe, Patrick Lahni, Basilia Zingarelli
Despite therapeutic advances in hemorrhagic shock, mortality from multiple organ failure remains high. AMP-activated protein kinase (AMPK) is involved in cellular energy homeostasis. Two catalytic subunits, α1 and α2, have been identified, with α1 subunit largely expressed in major organs. Here, we hypothesized that genetic deficiency of AMPKα1 worsens hemorrhage-induced multiple organ failure. We also investigated whether treatment with metformin, a clinically used drug for metabolic homeostasis, affords beneficial effects...
September 14, 2017: Shock
https://www.readbyqxmd.com/read/28913567/two-cell-embryos-are-more-sensitive-than-blastocysts-to-ampk-dependent-suppression-of-anabolism-and-stemness-by-commonly-used-fertility-drugs-a-diet-supplement-and-stress
#9
Alan Bolnick, Mohammed Abdulhasan, Brian Kilburn, Yufen Xie, Mindie Howard, Paul Andresen, Alexandra M Shamir, Jing Dai, Elizabeth E Puscheck, Eric Secor, Daniel A Rappolee
PURPOSE: This study tests whether metformin or diet supplement BR-DIM-induced AMP-activated protein kinase (AMPK) mediated effects on development are more pronounced in blastocysts or 2-cell mouse embryos. METHODS: Culture mouse zygotes to two-cell embryos and test effects after 0.5-1 h AMPK agonists' (e.g., Met, BR-DIM) exposure on AMPK-dependent ACCser79P phosphorylation and/or Oct4 by immunofluorescence. Culture morulae to blastocysts and test for increased ACCser79P, decreased Oct4 and for AMPK dependence by coculture with AMPK inhibitor compound C (CC)...
September 15, 2017: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/28911678/averrhoa-bilimbi-fruits-attenuate-hyperglycemia-mediated-oxidative-stress-in-streptozotocin-induced-diabetic-rats
#10
Surya B Kurup, S Mini
Hyperglycemia-mediated oxidative stress plays a major role in the development of diabetic complications. Averrhoa bilimbi Linn. (Oxalidaceae) is a medicinal plant with fruits reported to possess antidiabetic activity. This study evaluated the beneficial effects of the ethyl acetate fraction of A. bilimbi fruit (ABAEE) on the antioxidant/oxidant status in diabetes mellitus. Diabetic rats were treated orally with the ethyl acetate fraction of A. bilimbi fruits at a dose of 25 mg/kg body weight for 60 days. Serum glucose, glycated hemoglobin, plasma insulin, hepatic toxicity markers, antioxidant enzymes, lipid peroxidation products, and liver histopathology were assayed checked after 60 days of extract treatment...
April 2017: Journal of Food and Drug Analysis
https://www.readbyqxmd.com/read/28904527/cost-effectiveness-of-vildagliptin-versus-glimepiride-as-add-on-treatment-to-metformin-for-the-treatment-of-diabetes-mellitus-type-2-patients-in-greece
#11
Hara Kousoulakou, Magdalini Hatzikou, Varvara Baroutsou, John Yfantopoulos
OBJECTIVES: This study was designed to assess the cost-effectiveness of vildagliptin versus glimepiride as add-on to metformin in the management of type 2 diabetes mellitus (T2DM) patients in the Greek healthcare setting. METHODS: A cost-effectiveness model was designed, using MS Excel, to compare two treatment strategies. Strategy 1 consisted of first-line metformin, followed by metformin + vildagliptin in second-line, while strategy 2 consisted of first line metformin, followed by metformin + glimepiride in second line...
2017: Cost Effectiveness and Resource Allocation: C/E
https://www.readbyqxmd.com/read/28902377/-implementation-of-the-national-guidelines-for-the-treatment-of-diabetes-mellitus-type-2-in-secondary-diabetes-centers
#12
Lydia Marahrens, Daniel Röck, Tjalf Ziemssen, Raimar Kern, Focke Ziemssen, Andreas Fritsche
Background The German National Disease Management Guideline (NVL) on treatment of Type 2 Diabetes recommends lowering of blood glucose in four therapy steps. There is little evidence, how NVL is implemented for the individual patients. Methods 810 patients in secondary diabetes centers were examined within the DiabCheck(OCTplus) trial. Data about the patient's health status (electronic medical record) were classified according to the NVL treatment steps. The degree of implementation was assessed for every person with diabetes type 2 (NCT02 311 504)...
September 2017: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/28901251/case-report-severe-hematological-muscle-and-liver-toxicity-caused-by-drugs-and-artichoke-infusion-interaction-in-an-elderly-polymedicated-patient
#13
M G Campos, J Machado, M L Costa, S Lino, F Correia, F Maltez
Case report, in a patient with a history of diabetes and hypertension, treated with metformin, gliclazide, enalapril + hydrochlorothiazide, amlodipine, aspirin and diazepam, recently medicated for a gouty crisis with colchicine and clonixin without improvement. Believing it could help in the treatment of gouty crisis symptoms he took about 1.5 L of artichoke infusion (Cynara cardunculus). He felt better and did agriculture work but developed a distal muscle pain, severe anemia, standard biochemical liver cholestasis, increase of alkaline phosphatase and marked increase of inflammatory parameters (hyperleucocytosis) and enters in the emergency department at the hospital...
September 12, 2017: Current Drug Safety
https://www.readbyqxmd.com/read/28900501/metformin-sensitizes-leukemia-cells-to-vincristine-via-activation-of-amp-activated-protein-kinase
#14
Yong Yi, Linfeng Gao, Min Wu, Juan Ao, Chunyan Zhang, Xiaodong Wang, Min Lin, Johann Bergholz, Yujun Zhang, Zhi-Xiong Jim Xiao
Vincristine is extensively used chemotherapeutic medicine to treat leukemia. However, it remains a critical clinical problem with regard to its toxicity and drug-resistance. AMP-activated protein kinase (AMPK) is an energy sensor that is pivotal in maintaining cell metabolic homeostasis. It is reported that AMPK is involved in vincristine-induced apoptosis. However, whether AMPK is involved in chemotherapy-resistance is largely unclear. It is well-documented that metformin, a widely used medicine to treat type II diabetes, possesses anti-cancer activities, yet whether metformin affects leukemia cell viability via vincristine is unknown...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28894049/the-pathophysiological-basis-of-the-protective-effects-of-metformin-in-heart-failure
#15
Aleksandra Dziubak, Grażyna Wójcicka
Metformin, currently recommended as the drug of first choice in type 2 diabetes mellitus (T2DM), is one of the few antihiperglycemic drugs to reduce cardiovascular risk. Nonetheless, due to the risk of lactic acidosis during metformin therapy, its usage in patients with diabetes and heart failure (HF) is still a matter of debate. The aim of this review is to present data supporting the possibility of using metformin in the treatment of diabetic patients with concomitant heart failure. In the failing heart, metformin through the mechanism related to AMP-activated protein kinase (AMPK) activity, improves free fatty acids (FFA) and glucose metabolism, mitochondrial biogenesis, as well as nitric oxide (NO)-NO synthase pathway...
August 24, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28892924/comparison-of-pioglitazone-and-metformin-efficacy-against-glucocorticoid-induced-atherosclerosis-and-hepatic-steatosis-in-insulin-resistant-rats
#16
I M Nagendra Nayak, Koyagura Narendar, Patil Ashok M, M G Jamadar, V Hemanth Kumar
INTRODUCTION: Insulin Resistance is a major cause of Atherosclerosis (AS) and Non Alcoholic Fatty Liver Disease (NAFLD). These lipid alterations in blood vessels and liver may progress to cardiovascular abnormalities and cirrhosis respectively. Drugs like pioglitazone (PIO) and metformin (MET) are effective insulin sensitizers used in T2DM. But their efficacy and tolerability needs to be compared in IR associated abnormalities. AIM: To compare the efficacy of PIO and MET in glucocorticoid induced AS, Hepatic Steatosis (HS) and IR in albino rats...
July 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28883731/antipsychotic-associated-weight-gain-management-strategies-and-impact-on-treatment-adherence
#17
REVIEW
Madhubhashinee Dayabandara, Raveen Hanwella, Suhashini Ratnatunga, Sudarshi Seneviratne, Chathurie Suraweera, Varuni A de Silva
Antipsychotic-induced weight gain is a major management problem for clinicians. It has been shown that weight gain and obesity lead to increased cardiovascular and cerebrovascular morbidity and mortality, reduced quality of life and poor drug compliance. This narrative review discusses the propensity of various antipsychotics to cause weight gain, the pharmacologic and nonpharmacologic interventions available to counteract this effect and its impact on adherence. Most antipsychotics cause weight gain. The risk appears to be highest with olanzapine and clozapine...
2017: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/28881340/additional-benefits-of-routine-drugs-on-gastrointestinal-cancer-statins-metformin-and-proton-pump-inhibitors
#18
Moon Kyung Joo, Jong-Jae Park, Hoon Jai Chun
BACKGROUND: Commonly used medications including statins, metformin, and proton pump inhibitors (PPIs) effectively reduce the risk of esophageal, gastric, and colorectal cancer (CRC). SUMMARY: A number of observational studies and meta-analyses have shown that long-term statin use significantly reduces the incidence of gastrointestinal (GI) cancer. Moreover, statin use after GI cancer diagnosis has been significantly associated with better prognosis in large-scale cohort studies...
September 8, 2017: Digestive Diseases
https://www.readbyqxmd.com/read/28877452/meds-modify-microbiome-mediating-their-effects
#19
Nicole M Koropatkin, Eric C Martens
The mechanisms of action of some common medications remain unknown but, in some cases, may involve the microorganisms within us. A new study by Wu et al. (2017) provides evidence that the type 2 diabetes drug metformin alters the gut microbiota, which in turn may mediate some of the drug's effects.
September 5, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28877164/in-vivo-therapeutic-effect-of-combination-treatment-with-metformin-and-scutellaria-baicalensis-on-maintaining-bile-acid-homeostasis
#20
Kyungsun Han, Shambhunath Bose, Jing-Hua Wang, Soo-Kyoung Lim, Young-Won Chin, Young-Mi Kim, Han-Seok Choi, Hojun Kim
The radix of Scutellaria baicalensis (SB) is a herb widely used in traditional Chinese medicine to treat metabolic diseases. Several main components, including baicalin and wogonoside, possess anti-dyslipidemia, anti-obesity and anti-diabetic effects. We hypothesized that co-administration of SB extract and metformin exerts a better effect on obesity-induced insulin resistance and lipid metabolism than treatment with metformin alone. We compared the effect of metformin (100 mg/10 mL/kg/day) alone with co-administration of metformin (100 mg/5 mL/kg/day) and SB extract (200 mg/5 mL/kg/day) on Otsuka Long Evans Tokushima Fatty rats, a useful model of type II diabetes with obesity, and used Long-Evans Tokushima Otsuka rats as a control...
2017: PloS One
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