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Metformin AND Lactate

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https://www.readbyqxmd.com/read/28980449/high-volume-continuous-venovenous-hemodiafiltration-plus-resin-hemoperfusion-improve-severe-metformin-associated-toxicity
#1
Shuangxin Liu, Lixia Xu, Jianchao Ma, Renwei Huang, Ting Lin, Zhuo Li, Huabang Liang, Sijia Li, Ruizhao Li, Li Zhang, Yiming Tao, Zhilian Li, Yuanhan Chen, Zhiming Ye, Bin Zhang, Wenjian Wang, Houqing Xiao, Xinling Liang, Wei Shi
We present the case of a 42-year-old female patient who attempted suicide by taking approximately 100 tablets of metformin (500 mg). Laboratory tests revealed severe lactic acidosis with lactate levels of 24 mmol/L and pH of 7.09. The patient was treated with high-volume continuous venovenous hemodiafiltration (CVVH) and resin-sorbent hemoperfusion. Metformin concentrations were measured by high-performance liquid chromatography (HPLC) during CVVH and hemoperfusion treatment. Before extracorporeal treatment, plasma metformin concentration was 208...
October 5, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28940961/perioperative-continuation-of-metformin-does-not-improve-glycemic-control-in-patients-with-type-2-diabetes-a-randomized-controlled-trial
#2
A H Hulst, J A W Polderman, E Ouweneel, A J Pijl, M W Hollmann, J H DeVries, B Preckel, J Hermanides
Historically, metformin was withheld before surgery in fear of metformin associated lactic acidosis. Now, this risk is deemed low and guidelines move towards continuation of metformin. We hypothesized that continuing metformin perioperatively would lower postoperative serum glucose without an effect on plasma lactate. We performed a single-blind multicenter RCT in type 2 diabetes mellitus patients scheduled for non-cardiac surgery and continued (MF+) or withheld (MF-) metformin before surgery. Main outcome parameters were the differences in perioperative plasma glucose and lactate levels...
September 20, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28936623/acute-renal-metabolic-effect-of-metformin-assessed-with-hyperpolarised-mri-in-rats
#3
Haiyun Qi, Per M Nielsen, Marie Schroeder, Lotte B Bertelsen, Fredrik Palm, Christoffer Laustsen
AIMS/HYPOTHESIS: Metformin inhibits hepatic mitochondrial glycerol phosphate dehydrogenase, thereby increasing cytosolic lactate and suppressing gluconeogenesis flux in the liver. This inhibition alters cytosolic and mitochondrial reduction-oxidation (redox) potential, which has been reported to protect organ function in several disease states including diabetes. In this study, we investigated the acute metabolic and functional changes induced by metformin in the kidneys of both healthy and insulinopenic Wistar rats used as a model of diabetes...
September 21, 2017: Diabetologia
https://www.readbyqxmd.com/read/28923861/mct1-inhibitor-azd3965-increases-mitochondrial-metabolism-facilitating-combination-therapy-and-non-invasive-magnetic-resonance-spectroscopy
#4
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/28915221/metformin-exerts-beneficial-effects-in-hemorrhagic-shock-in-an-ampk%C3%AE-1-independent-manner
#5
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/28867217/in-utero-and-lactational-exposure-to-metformin-induces-reproductive-alterations-in-male-rat-offspring
#6
Simone Forcato, Daniella Regina Barrionuevo da Silva Novi, Nathalia Orlandini Costa, Lorena Ireno Borges, Maria Luiza Marino de Góes, Graziela Scalianti Ceravolo, Daniela Cristina Ceccatto Gerardin
Metformin (MET) is prescribed for the treatment of type 2 diabetes mellitus and gestational diabetes. Although MET crosses the placenta, it is considered safe throughout gestation. However, it has been shown in humans that maternal exposure to MET increases sex hormone binding globulin levels in newborns, and in rats it decreases the testosterone concentration at gestational day (GD) 16.5. Therefore, the present study evaluated if maternal exposure to MET could interfere with reproductive parameters of male offspring...
September 1, 2017: Reproductive Toxicology
https://www.readbyqxmd.com/read/28836132/lactate-levels-with-chronic-metformin-use-a-narrative-review
#7
REVIEW
Weiyi Huang, Ronald L Castelino, Gregory M Peterson
Metformin has been associated with lactic acidosis. Lactate levels are not commonly tested in clinical practice, and it is unclear to what extent metformin would typically increase lactate levels with chronic use. The aim of this review was to determine whether regular monitoring of the plasma lactate level would be beneficial in avoiding lactate accumulation and, ultimately, minimising the incidence of lactic acidosis in metformin-treated patients.A comprehensive search of PubMed, Embase, Web of Science, Cochrane and International Pharmaceutical Abstracts databases covering the period up to 30 May 2017 was performed...
November 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/28816632/the-liver-circadian-clock-modulates-biochemical-and-physiological-responses-to-metformin
#8
Emma Henriksson, Anne-Laure Huber, Erin K Soto, Anna Kriebs, Megan E Vaughan, Drew Duglan, Alanna B Chan, Stephanie J Papp, Madelena Nguyen, Megan E Afetian, Katja A Lamia
Metformin is widely used in the treatment of type 2 diabetes to lower blood glucose. Although metformin is a relatively safe and effective drug, its clinical efficacy is variable and under certain circumstances it may contribute to life-threatening lactic acidosis. Thus, additional understanding of metformin pharmacokinetics and pharmacodynamics could provide important information regarding therapeutic use of this widely prescribed drug. Here we report a significant effect of time of day on acute blood glucose reduction in response to metformin administration and on blood lactate levels in healthy mice...
August 2017: Journal of Biological Rhythms
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
#9
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/28731890/metformin-exposure-during-pregnancy-and-lactation-did-not-cause-vascular-reactivity-alteration-in-adult-male-offspring
#10
Daniella R B S Novi, Simone Forcato, Camila B Vidigal, Guilherme H Loiola, Daniela C C Gerardin, Graziela S Ceravolo
Metformin has been used for the treatment of some metabolic diseases during gestation and the beneficial effects of metformin to the vascular system have been described in diabetic and obese animal models. Nevertheless, the long term consequences to the vascular system of offspring maternally exposed to metformin have not yet been characterized. Therefore, we want to test the hypothesis that gestational and lactational exposure to metformin would be safe for the vascular reactivity of male adult offspring. Wistar female rats were treated with metformin 293mg/kg/day, by gavage, from gestational day (GD) 0 to GD 21 (METG) or GD 0 until post natal day (PND) 21 (METGL)...
July 19, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28728159/oxamate-enhances-the-anti-inflammatory-and-insulin-sensitizing-effects-of-metformin-in-diabetic-mice
#11
Mu-Chao Wu, Wei-Ran Ye, Yi-Jia Zheng, Shan-Shan Zhang
Metformin (MET) is the first-line drug for treating type 2 diabetes mellitus (T2DM). However, MET increases blood lactate levels in patients with T2DM. Lactate possesses proinflammatory properties and causes insulin resistance (IR). Oxamate (OXA), a lactate dehydrogenase inhibitor, can decrease tissue lactate production and blood lactate levels. This study was conducted to examine the effects of the combination of OXA and MET on inflammation, and IR in diabetic db/db mice. Supplementation of OXA to MET led to lowered tissue lactate production and serum lactate levels compared to MET alone, accompanied with further decreased tissue and blood levels of pro-inflammatory cytokines, along with better insulin sensitivity, beta-cell mass, and glycemic control in diabetic db/db mice...
July 21, 2017: Pharmacology
https://www.readbyqxmd.com/read/28702329/metformin-causes-a-futile-intestinal-hepatic-cycle-which-increases-energy-expenditure-and-slows-down-development-of-a-type-2-diabetes-like-state
#12
Philipp Schommers, Anna Thurau, Insa Bultmann-Mellin, Maria Guschlbauer, Andreas R Klatt, Jan Rozman, Martin Klingenspor, Martin Hrabe de Angelis, Jens Alber, Dirk Gründemann, Anja Sterner-Kock, Rudolf J Wiesner
OBJECTIVE: Metformin, the first line drug for treatment of type 2 diabetes, suppresses hepatic gluconeogenesis and reduces body weight in patients, the latter by an unknown mechanism. METHODS: Mice on a high fat diet were continuously fed metformin in a therapeutically relevant dose, mimicking a retarded formulation. RESULTS: Feeding metformin in pharmacologically relevant doses to mice on a high fat diet normalized HbA1c levels and ameliorated glucose tolerance, as expected, but also considerably slowed down weight gain...
July 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28693440/serum-lactate-level-and-mortality-in-metformin-associated-lactic-acidosis-requiring-renal-replacement-therapy-a-systematic-review-of-case-reports-and-case-series
#13
Hung-Chieh Yeh, I-Wen Ting, Ching-Wei Tsai, Jenn-Yu Wu, Chin-Chi Kuo
BACKGROUND: The current practice concerning timing, mode, and dose of renal replacement therapy (RRT) in patients with metformin-associated lactic acidosis (MALA) with renal failure remains unknown. To investigate whether serum lactate level and prescription pattern of RRT are associated with mortality in patients with MALA requiring RRT. METHODS: We searched PubMed/Medline and EMBASE from inception to Sep 2014 and applied predetermined exclusion criteria. Case-level data including case's demographics and clinical information related to MALA were abstracted...
July 10, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28688035/metformin-accelerates-glycolytic-lactate-production-in-cultured-primary-cerebellar-granule-neurons
#14
Eva-Maria Blumrich, Ralf Dringen
Metformin is the most frequently used drug for the treatment of type-II diabetes. As metformin has been reported to cross the blood-brain barrier, brain cells will encounter this drug. To test whether metformin may affect the metabolism of neurons, we exposed cultured rat cerebellar granule neurons to metformin. Treatment with metformin caused a time- and concentration-dependent increase in glycolytic lactate release from viable neurons as demonstrated by the three-to fivefold increase in extracellular lactate concentration determined after exposure to metformin...
July 7, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28656086/berberine-protects-against-metformin-associated-lactic-acidosis-in-induced-diabetes-mellitus
#15
Suhail Ahmed Almani, Iqbal Ahmed Memon, Tariq Zaffar Shaikh, Haji Khan Khoharo, Ikramuddin Ujjan
OBJECTIVES: Causality of occurrence of metformin-associated lactic acidosis (MALA) is a clinical problem. Currently, there is no drug available to prevent MALA. The present study was conducted to evaluate the protective effect of Berberine (BBR) against MALA in induced diabetic rat model. MATERIALS AND METHODS: A sample of 75 healthy male Wistar rats was randomly selected according to inclusion and exclusion criteria. 75 male Wistar rats were randomly divided into a control and 4 experimental groups...
May 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28632474/evaluation-of-the-concurrent-use-of-dolutegravir-and-metformin-in-human-immunodeficiency-virus-infected-patients
#16
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/28606929/targeting-oxygen-sensing-prolyl-hydroxylase-for-metformin-associated-lactic-acidosis-treatment
#17
Tomoko Oyaizu-Toramaru, Tomohiro Suhara, Noriyo Hayakawa, Takashi Nakamura, Akiko Kubo, Shizuka Minamishima, Kyoji Yamaguchi, Takako Hishiki, Hiroshi Morisaki, Makoto Suematsu, Yoji Andrew Minamishima
Metformin is one of the most widely used therapeutics for type 2 diabetes mellitus and also has anticancer and antiaging properties. However, it is known to induce metformin-associated lactic acidosis (MALA), a severe medical condition with poor prognosis, especially in individuals with renal dysfunction. Inhibition of prolyl hydroxylase (PHD) is known to activate the transcription factor hypoxia-inducible factor (HIF) that increases lactate efflux as a result of enhanced glycolysis, but it also enhances gluconeogenesis from lactate in the liver that contributes to reducing circulating lactate levels...
August 15, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28581641/clk1-regulated-aerobic-glycolysis-is-involved-in-glioma-chemoresistance
#18
Li Zhang, Huicui Yang, Wenbin Zhang, Zhongqin Liang, Qiang Huang, Guoqiang Xu, Xuechu Zhen, Long Tai Zheng
Chemoresistance remains a major challenge for the treatment of glioma. In this study, we investigated the role of Clock 1 (Clk1), which encodes an enzyme that is necessary for ubiquinone biosynthesis in glioma chemoresistance in vitro. The results showed that Clk1 was highly expressed in GL261 mouse glioma cells which were most sensitive to 1,3Bis (2-chloroethyl) 1 nitrosourea (BCNU) while was low expressed in BCNU resistant cells such as glioma cancer stem cells, T98G, U87MG and U251 glioma cells. Knockdown of Clk1 in GL261 glioma cells significantly reduced BCNU- or cisplatin-induced cell apoptosis, whereas the proliferative activity and the expression of multidrug resistance-related genes including MDR1, O6-methylguanine-DNA methyltransferase, and GSTP1 were not changed...
August 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28579457/metformin-ameliorates-gender-and-age-dependent-hemodynamic-instability-and-myocardial-injury-in-murine-hemorrhagic-shock
#19
Dzmitry Matsiukevich, Giovanna Piraino, Patrick Lahni, Paul W Hake, Vivian Wolfe, Michael O'Connor, Jeanne James, Basilia Zingarelli
Severity of multiple organ failure is significantly impacted by age and gender in patients with hemorrhagic shock. However, the molecular mechanisms underlying the enhanced organ injury are not fully understood. AMP-activated protein kinase (AMPK) is a pivotal orchestrator of metabolic responses during stress. We investigated whether hemorrhage-induced myocardial injury is age and gender dependent and whether treatment with metformin, an AMPK activator, affords cardioprotective effects. C57/BL6 young (3-5months) and mature (9-12months) male and female mice were subjected to hemorrhagic shock by blood withdrawing followed by resuscitation with blood and Lactated Ringer's solution...
June 1, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28571222/the-effect-of-metformin-as-an-adjunct-therapy-in-adolescents-with-type-1-diabetes
#20
Aria Setoodeh, Abdollah Didban, Ali Rabbani, Azadeh Sayarifard, Farzaneh Abbasi, Fatemeh Sayarifard, Fatemeh Hoseinzade
INTRODUCTION: The strict control of blood glucose levels in adolescents with Type 1 Diabetes Mellitus (T1DM) is accompanied with a considerable long term decrease in microvasular and macrovascular complications. AIM: This study was conducted to investigate the effect of metformin as an adjunct therapy in adolescents with poorly controlled Type 1 diabetes. MATERIALS AND METHODS: It was a quasi-experimental (an uncontrolled before and after) study...
April 2017: Journal of Clinical and Diagnostic Research: JCDR
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