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Metformin AND Lactate

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https://www.readbyqxmd.com/read/29658305/liver-antioxidant-and-aerobic-status-improves-after-metformin-and-melatonin-administration-in-a-rat-model-of-high-fat-diet-and-mammary-carcinogenesis
#1
Natalia Kurhaluk, Bianka Bojková, Pawel J Winklewski
Oxidative stress is involved in the development of various cancers. In the present study the effect of long-term administration of peroral antidiabetic metformin and pineal hormone melatonin on liver antioxidant and aerobic status in female Sprague-Dawley rats carrying mammary tumors induced by N-methyl-N-nitrosourea was evaluated. Both substances were administered in a preventive/curative manner (12 days before and 16 weeks after the carcinogen application). Carcinogen administration induced oxidative stress: the level of thiobarbituric acid reactive products (TBARS) as a marker of reactive oxygen species (ROS) generation in liver increased as well as the level of oxidatively modified protein content (OMP, aldehyde and ketone derivates)...
April 15, 2018: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/29614026/prenatal-metformin-therapy-attenuates-hypertension-of-developmental-origin-in-male-adult-offspring-exposed-to-maternal-high-fructose-and-post-weaning-high-fat-diets
#2
You-Lin Tain, Kay L H Wu, Wei-Chia Lee, Steve Leu, Julie Y H Chan
Widespread consumption of a Western diet, comprised of highly refined carbohydrates and fat, may play a role in the epidemic of hypertension. Hypertension can take origin from early life. Metformin is the preferred treatment for type 2 diabetes. We examined whether prenatal metformin therapy can prevent maternal high-fructose plus post-weaning high-fat diets-induced hypertension of developmental origins via regulation of nutrient sensing signals, uric acid, oxidative stress, and the nitric oxide (NO) pathway...
April 3, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29609531/metformin-associated-lactic-acidosis-a-case-series-of-28-patients-treated-with-sustained-low-efficiency-dialysis-sled-and-long-term-follow-up
#3
Andrea Angioi, Gianfranca Cabiddu, Maura Conti, Gianfranco Pili, Alice Atzeni, Valeria Matta, Riccardo Cao, Matteo Floris, Marco Songini, Maria Franca Mulas, Mitchell Rosner, Antonello Pani
BACKGROUND: Metformin associated lactic acidosis (MALA) is a well-known serious side effect of biguanides. However, the best treatment strategy remains a matter of debate. In the last 14 years, we observed a significant increase in hospitalizations for MALA to our Center. We report the outcomes of our clinical and therapeutic approach. METHODS: This is a single-center case series. Twenty-eight patients affected with MALA and acute kidney failure admitted between January 2000 and September 2014 were included...
April 2, 2018: BMC Nephrology
https://www.readbyqxmd.com/read/29609037/%C3%AE-cyano-4-hydroxycinnamate-impairs-pancreatic-cancer-cells-by-stimulating-the-p38-signaling-pathway
#4
Maria Schönrogge, Hagen Kerndl, Xianbin Zhang, Simone Kumstel, Brigitte Vollmar, Dietmar Zechner
Multiple studies are currently targeting dysregulated cancer cell metabolism with distinct combinations of inhibitors. In this study, we evaluated in pancreatic cancer cells metformin, which blocks oxidative phosphorylation, in combination with α-cyano-4-hydroxycinnamate, which has been reported to inhibit the export of lactate from the cytosol. The combination of metformin with α-cyano-4-hydroxycinnamate had a major inhibitory effect on the migration of 6606PDA cells. Monotherapy with α-cyano-4-hydroxycinnamate and especially the combination with metformin also caused significant inhibition of cell proliferation and induced cell death...
March 30, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29574345/range-of-therapeutic-metformin-concentrations-in-clinical-blood-samples-and-comparison-to-a-forensic-case-with-death-due-to-lactic-acidosis
#5
C Hess, M Unger, B Madea, B Stratmann, D Tschoepe
Due to a lack of reference values for blood concentration of metformin in the literature, the forensic evaluation of metformin findings in blood samples is difficult. Interpretations with regard to the assessment of blood concentrations as well as an estimation of the ingested metformin amounts are often vague. Furthermore, post mortem evaluation of death due to lactic acidosis because of metformin is difficult since renal performance or lactate concentrations can not always reliably be determined after death...
March 12, 2018: Forensic Science International
https://www.readbyqxmd.com/read/29550639/effect-of-metformin-on-estrogen-and-progesterone-receptor-positive-mcf-7-and-triple-negative-mda-mb-231-breast-cancer-cells
#6
Inês Amaral, Cláudia Silva, Ana Correia-Branco, Fátima Martel
This work aimed to investigate the effect of metformin on cellular glucose uptake and metabolism by breast cancer cells, as a mechanism contributing to its anticancer properties. Estrogen and progesterone receptor-positive (MCF-7) and triple-negative (MDA-MB-231) breast cancer cell lines were used as in vitro models of breast cancer. Short-term (26 min) exposure of MCF-7 and MDA-MB-231 cells to metformin inhibited uptake of3 H-deoxy-D-glucose (3 H-DG). In contrast, long-term (24 h) exposure to metformin (5 μM-1 mM) concentration-dependently increased3 H-DG uptake in both cell lines...
March 15, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29534338/-massive-metformin-overdose
#7
Angela L Chiew, Daniel F B Wright, Nicola M Dobos, Kylie McArdle, Ahmed A Mostafa, Annemarie Newth, Michael S Roberts, Geoffrey K Isbister
Massive metformin overdose can cause metabolic acidosis with hyperlactatemia. A 55-year-old female presented 5h post multi-drug overdose, including 132 g extended-release metformin. Continuous venovenous haemodiafiltration (CVVHDF) and noradrenaline were commenced due to metabolic acidosis (pH 7.0, lactate 17 mmol/L) and shock. Despite 3 hours of CVVHDF, her acidosis worsened (pH 6.83, lactate 24 mmol/L). Intermittent haemodialysis(IHD) improved acidosis (pH 7.13, lactate 26 mmol/l), but again worsened (pH 6...
March 13, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29520235/lactate-induced-glucose-output-is-unchanged-by-metformin-at-a-therapeutic-concentration-a-mass-spectrometry-imaging-study-of-the-perfused-rat-liver
#8
Giulio Calza, Elisabeth Nyberg, Matias Mäkinen, Rabah Soliymani, Annunziata Cascone, Dan Lindholm, Emanuele Barborini, Marc Baumann, Maciej Lalowski, Ove Eriksson
Metformin is the first line drug for type 2 diabetes but its molecular mechanisms remain unclear. Here, we have studied the acute effect of a therapeutically relevant intrahepatic concentration of metformin on glucose production from lactate. We selected the perfused rat liver as experimental system since it enables the complete control of drug dosage. We used MALDI (matrix-assisted laser desorption/ionization) mass spectrometry imaging to estimate the concentration of metformin in the livers and we measured the concentration of glucose in the effluent medium under basal conditions and following lactate addition...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29484415/metformin-facilitates-bg45%C3%A2-induced-apoptosis-via-an-anti%C3%A2-warburg-effect-in-cholangiocarcinoma-cells
#9
Dehua Tang, Lei Xu, Mingming Zhang, Robert Gregory Dorfman, Yida Pan, Qian Zhou, Lixing Zhou, Yuming Wang, Yang Li, Yuyao Yin, Lei Wang, Xiaoping Zou
Cholangiocarcinoma (CCA) is a highly lethal malignancy with an often late diagnosis and consequent poor prognosis. Chemotherapy is the only therapeutic strategy for most patients. Compared to normal cells, tumor cells preferentially metabolize glucose to lactate, even in aerobic conditions. Such metabolic alterations not only support the growth and invasion of tumor cells, but also promote their chemoresistance. The purpose of our study was to explore the role of metformin in regulating the metabolism of CCA, as well as to investigate whether metformin could act as a chemosensitizer of the HDAC3 inhibitor BG45, and therefore have potential for the treatment of CCA...
February 20, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29465046/clinical-and-laboratory-features-of-metformin-intoxication-in-suicidal-patients-attending-an-intensive-care-unit
#10
A Cetinkaya, D Avci, A Erden, O Akca, O Ozer, U Kalan, A I Gunal
Introduction: This study has been performed for the purpose of researching the complications occurred at patients who took metformin overdose in an attempt to suicide. None of the patients has the diagnosis of diabetes mellitus and never used metformin. Materials and Methods: This retrospective cross-sectional study was carried out with 21 patients who has neither diagnosed diabetes mellitus nor taken metformin for suicide before. Results: It was observed that there is a moderate, negative (r = -0...
February 2018: Nigerian Journal of Clinical Practice
https://www.readbyqxmd.com/read/29457876/pharmacokinetics-of-metformin-in-patients-with-gastrointestinal-intolerance
#11
L McCreight, T B Stage, P Connelly, M Lonergan, F Nielsen, C Prehn, J Adamski, K Brosen, E R Pearson
AIMS: Metformin intolerance symptoms are gastrointestinal in nature, but the underlying mechanism is poorly understood. The aim of this study was to assess potential causes of metformin intolerance including: altered metformin uptake from the intestine; increased anaerobic glucose utilisation and subsequent lactate production; altered serotonin uptake; and altered bile acid pool. METHODS: This pharmacokinetic study recruited ten severely intolerant and ten tolerant individuals matched for age, sex and BMI...
February 19, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29456175/metformin-induced-lactic-acidosis-mila-a-case-report-and-review-of-current-diagnostic-paradigm
#12
Lauren Krowl, Hassan Al-Khalisy, Pratibha Kaul
A new diagnostic paradigm has been proposed to better categorize causes of Metformin-Associated Lactic Acidosis (MALA). The diagnostic criteria defines a link between Metformin and lactic acidosis if lactate is >5mmol/L, Ph<7.35 and Metformin assay >5mg/L. Metformin assays are not readily available in emergency departments including nationwide Veteran's Affairs Hospitals; thereby making this proposed classification tool difficult to use in today's clinical practice. We describe a case report of a 45-year-old male, who took twice the amount of Metformin prescribed and presented with Metformin-induced lactic acidosis...
February 15, 2018: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/29427160/metformin-associated-lactic-acidosis-a-case-report
#13
Takehide Umeda, Taro Minami, Keith Bartolomei, Eleanor Summerhill
A 54-year-old woman with type 2 diabetes mellitus, hypertension, and peripheral vascular disease developed life-threatening lactic acidosis during treatment with metformin for type 2 diabetes. The woman received metformin at 1000 mg orally twice a day for type 2 diabetes. She presented to our emergency department with a 3-day history of severe watery diarrhea, nausea, and vomiting. Her grandson whom she cared for had gastroenteritis several days prior to the onset of her symptoms. She was confused and hypotensive with a blood pressure of 70/39 mmHg...
February 9, 2018: Drug Safety—Case Reports
https://www.readbyqxmd.com/read/29386513/hexokinase-2-depletion-inhibits-glycolysis-and-induces-oxidative-phosphorylation-in-hepatocellular-carcinoma-and-sensitizes-to-metformin
#14
Dannielle DeWaal, Veronique Nogueira, Alexander R Terry, Krushna C Patra, Sang-Min Jeon, Grace Guzman, Jennifer Au, Christopher P Long, Maciek R Antoniewicz, Nissim Hay
Hepatocellular carcinoma (HCC) cells are metabolically distinct from normal hepatocytes by expressing the high-affinity hexokinase (HK2) and suppressing glucokinase (GCK). This is exploited to selectively target HCC. Hepatic HK2 deletion inhibits tumor incidence in a mouse model of hepatocarcinogenesis. Silencing HK2 in human HCC cells inhibits tumorigenesis and increases cell death, which cannot be restored by GCK or mitochondrial binding deficient HK2. Upon HK2 silencing, glucose flux to pyruvate and lactate is inhibited, but TCA fluxes are maintained...
January 31, 2018: Nature Communications
https://www.readbyqxmd.com/read/29318219/extending-metformin-use-in-diabetic-kidney-disease-a-pharmacokinetic-study-in-stage-4-diabetic-nephropathy
#15
Ajith Munasinghe Dissanayake, Mark Christopher Wheldon, Jafar Ahmed, Christopher John Hood
Introduction: Metformin use in advanced chronic kidney disease is controversial. This study sought to examine the pharmacokinetics, safety, and efficacy of low-dose metformin in patients with type 2 diabetes and stage 4 chronic kidney disease. Methods: In this open-label, phase I trial, 3 consecutive cohorts (1, 2, and 3) of 6 patients each were recruited to receive 250-, 500-, or 1000-mg once-daily doses of metformin, respectively. All patients underwent a first-dose pharmacokinetic profile and weekly trough metformin concentrations for the duration of 4 weeks of daily therapy...
July 2017: KI Reports
https://www.readbyqxmd.com/read/29305402/metformin-treatment-in-patients-with-type-2-diabetes-and-chronic-kidney-disease-stages-3a-3b-or-4
#16
Jean-Daniel Lalau, Farshad Kajbaf, Youssef Bennis, Anne-Sophie Hurtel-Lemaire, Frans Belpaire, Marc E De Broe
OBJECTIVE: This study was conducted to define a safe, effective dose regimen for metformin in moderate and severe chronic kidney disease (CKD; stages 3A/3B and 4, respectively), after the lifting of restrictions on metformin use in patients with diabetes with moderate-to-severe CKD in the absence of prospective safety and efficacy studies. RESEARCH DESIGN AND METHODS: Three complementary studies were performed: 1 ) a dose-finding study in CKD stages 1-5, in which blood metformin concentrations were evaluated during a 1-week period after each dose increase; 2 ) a 4-month metformin treatment study for validating the optimal metformin dose as a function of the CKD stage (3A, 3B, and 4), with blood metformin, lactate, and HbA1c concentrations monitored monthly; and 3 ) an assessment of pharmacokinetic parameters after the administration of a single dose of metformin in steady-state CKD stages 3A, 3B, and 4...
March 2018: Diabetes Care
https://www.readbyqxmd.com/read/29260243/-perioperative-handling-of-antidiabetic-drugs
#17
REVIEW
J Wagner, V Luber, J F Lock, U A Dietz, S Lichthardt, N Matthes, K Krajinovic, C-T Germer, S Knop, A Wiegering
Diabetes mellitus is the most frequent metabolic disorder in the western world with a prevalence of 3% in adults under 65 years of age and 14.3% in adults over 65 years of age. Due to the increasing age of our population, the number of patients taking oral antidiabetic drugs has increased. Thus, operating physicians must make a risk-adapted decision whether the medication can be continued perioperatively or if certain drugs must be paused, and if so, with what risks. Operative interventions can lead to a number of metabolic shifts, which change the normal glucose metabolism...
February 2018: Der Chirurg; Zeitschrift Für Alle Gebiete der Operativen Medizen
https://www.readbyqxmd.com/read/29198069/does-metformin-exposure-before-icu-stay-have-any-impact-on-patients-outcome-a-retrospective-cohort-study-of-diabetic-patients
#18
Sebastien Jochmans, Jean-Emmanuel Alphonsine, Jonathan Chelly, Ly Van Phach Vong, Oumar Sy, Nathalie Rolin, Olivier Ellrodt, Mehran Monchi, Christophe Vinsonneau
BACKGROUND: Impact of metformin exposure before ICU stay remains controversial. Metformin is thought to induce lactic acidosis and haemodynamic instability but may reduce ICU mortality. We evaluated its influence on outcome in diabetic patients admitted in the ICU and then compared two different populations based on the presence of septic shock. METHODS: We conducted a retrospective cohort study in a 24-bed French ICU between October 2010 and December 2013, including all ICU-admitted diabetic patients...
December 2, 2017: Annals of Intensive Care
https://www.readbyqxmd.com/read/29163155/intracellular-hyper-acidification-potentiated-by-hydrogen-sulfide-mediates-invasive-and-therapy-resistant-cancer-cell-death
#19
Zheng-Wei Lee, Xin-Yi Teo, Zhi J Song, Dawn S Nin, Wisna Novera, Bok A Choo, Brian W Dymock, Philip K Moore, Ruby Y-J Huang, Lih-Wen Deng
Slow and continuous release of H2 S by GYY4137 has previously been demonstrated to kill cancer cells by increasing glycolysis and impairing anion exchanger and sodium/proton exchanger activity. This action is specific for cancer cells. The resulting lactate overproduction and defective pH homeostasis bring about intracellular acidification-induced cancer cell death. The present study investigated the potency of H2 S released by GYY4137 against invasive and radio- as well as chemo-resistant cancers, known to be glycolytically active...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29142469/hypothermic-machine-perfusion-with-metformin-university-of-wisconsin-solution-for-ex-viv-o-preservation-of-standard-and-marginal-liver-grafts-in-a-rat-model
#20
Yi-Chao Chai, Guo-Xin Dang, Hai-Qi He, Jian-Hua Shi, Hong-Ke Zhang, Rui-Tao Zhang, Bo Wang, Liang-Shuo Hu, Yi Lv
AIM: To compare the effect of University of Wisconsin (UW) solution with or without metformin, an AMP-activated protein kinase (AMPK) activator, for preserving standard and marginal liver grafts of young and aged rats ex vivo by hypothermic machine perfusion (HMP). METHODS: Eighteen young (4 mo old) and 18 aged (17 mo old) healthy male SD rats were selected and randomly divided into three groups: control group, UW solution perfusion group (UWP), and UW solution with metformin perfusion group (MUWP)...
October 28, 2017: World Journal of Gastroenterology: WJG
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