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metformin drug

Corina T Madreiter-Sokolowski, Armin A Sokolowski, Markus Waldeck-Weiermair, Roland Malli, Wolfgang F Graier
Senescence is related to the loss of cellular homeostasis and functions, which leads to a progressive decline in physiological ability and to aging-associated diseases. Since mitochondria are essential to energy supply, cell differentiation, cell cycle control, intracellular signaling and Ca2+ sequestration, fine-tuning mitochondrial activity appropriately, is a tightrope walk during aging. For instance, the mitochondrial oxidative phosphorylation (OXPHOS) ensures a supply of adenosine triphosphate (ATP), but is also the main source of potentially harmful levels of reactive oxygen species (ROS)...
March 16, 2018: Genes
Lisa Menegazzo, Valentina Scattolini, Roberta Cappellari, Benedetta Maria Bonora, Mattia Albiero, Mario Bortolozzi, Filippo Romanato, Giulio Ceolotto, Saula Vigili de Kreutzeberg, Angelo Avogaro, Gian Paolo Fadini
AIMS: Diabetes is associated with an excess release of neutrophil extracellular traps (NETs) and an enhanced NETosis, a neutrophil cell death programme instrumental to anti-microbial defences, but also involved in tissue damage. We herein investigated whether the antidiabetic drug metformin protects against NETosis. METHODS: We measured NET components in the plasma of patients with pre-diabetes who were randomized to receive metformin or placebo for 2 months. To control for the effect on glucose, we also measured NET components in the plasma of patients with type 2 diabetes before and after treatment with insulin or dapagliflozin...
March 15, 2018: Acta Diabetologica
Stephen Safe, James L Abbruzzese, Maen Abdelrahim, Erik Hedrick
Specificity protein (Sp) transcription factors (TFs) such as Sp1 are critical for early development but their expression decreases with age and there is evidence that transformation of normal cells to cancer cells is associated with upregulation of Sp1, Sp3 and Sp4 which are highly expressed in cancer cells and tumors. Sp1 is a negative prognostic factor for pancreatic, colon, glioma, gastric, breast, prostate, and lung cancer patients. Functional studies also demonstrate that Sp TFs regulate genes responsible for cancer cell growth, survival, migration/invasion, inflammation and drug resistance, and Sp1, Sp3 and Sp4 are also non-oncogene addiction (NOA) genes and important drug targets...
March 15, 2018: Cancer Prevention Research
Antonio Gil-Gomez, Ana Isabel Gómez-Sotelo, Isidora Ranchal, Ángela Rojas, Marta García-Valdecasas, Rocío Muñoz-Hernández, Rocío Gallego-Durán, Javier Ampuero, Manuel Romero Gómez
AIM: to analyze the effect of metformin on ammonia production derived from glutamine metabolism in vitro and in vivo. METHODS: twenty male Wistar rats were studied for 28 days after a porto-caval anastomosis (n = 16) or a sham operation (n = 4). Porto-caval shunted animals were randomized into two groups (n = 8) and either received 30 mg/kg/day of metformin for two weeks or were control animals. Plasma ammonia concentration, Gls gene expression and K-type glutaminase activity were measured in the small intestine, muscle and kidney...
March 15, 2018: Revista Española de Enfermedades Digestivas
Balraj Singh, Vanessa N Sarli, Laura J Washburn, Milan R Raythatha, Anthony Lucci
We previously described a strategy for selecting highly adaptable rare triple-negative breast cancer (TNBC) cells based on their ability to survive a severe and prolonged metabolic challenge, e.g., a lack of glutamine. We hypothesized that metabolically adaptable (MA) cancer cells selected from the SUM149 cell line in this manner have the capacity to survive a variety of challenges that postulated "decathlon winner" cancer cells must survive to succeed in metastasis. These MA cells were resistant to glutaminase inhibitor CB-839, as predicted from their ability to proliferate without exogenous glutamine...
February 16, 2018: Oncotarget
Davide Di Fusco, Vincenzo Dinallo, Ivan Monteleone, Federica Laudisi, Irene Marafini, Eleonora Franzè, Antonio Di Grazia, Rami Dwairi, Alfredo Colantoni, Angela Ortenzi, Carmine Stolfi, Giovanni Monteleone
Metformin, a hypoglycemic drug used for treatment of type 2 diabetes, regulates also inflammatory pathways. By using several models of intestinal inflammation, we examined whether metformin exerts anti-inflammatory effects and investigated the basic mechanism by which metformin blocks pathologic signals. Colitic mice given metformin exhibited less colonic inflammation and increased expression of active AMP-activated protein kinase, a mediator of the metabolic effects of metformin, in both epithelial and lamina propria compartments...
March 14, 2018: Clinical Science (1979-)
Ye-Jin Lee, Sung Koo Han, Ju Hee Park, Jung Kyu Lee, Deog Keom Kim, Hee Soon Chung, Eun Young Heo
Background/Aims: Patients with diabetes mellitus (DM) and tuberculosis (TB) have increased morbidity and a high risk of treatment failure or recurrence. It is important to manage both diseases simultaneously. Among anti-diabetic drugs, metformin inhibits intracellular growth of mycobacteria. Therefore, we examined the effects of metformin on TB treatment, especially in patients with DM. Methods: This retrospective cohort study included patients with culture-positive pulmonary TB diagnosed between 2011 and 2012...
March 16, 2018: Korean Journal of Internal Medicine
Sanjay Kalra, Jubbin Jacob, Manash P Baruah
Salutogenesis is an accepted approach for chronic disease management. Calorie restriction and exercise are two evidence based salutogenic interventions in diabetes treatment. Calorie restriction mimetics and exercise mimetics may be used as pharmacological tools to help manage diabetes in a sulutogenic manner. This article discusses the biochemical basis and pharmacology of metformin and sodium glucose cotransporter 2 inhibitors. It describes how a combination of these drugs can be used as a calories restriction and exercise mimetic, to help improve diabetes control...
January 2018: Indian Journal of Endocrinology and Metabolism
Eunyoung Bang, Boyoung Lee, Joon-Oh Park, Yooncheol Jang, Aekyong Kim, Sungwuk Kim, Hee-Sup Shin
In recent years, as the aging population grows, aging-induced cognitive impairments including dementia and Alzheimer's disease (AD) have become the biggest challenges for global public health and social care. Therefore, the development of potential therapeutic drugs for aging-associated cognitive impairment is essential. Metabolic dysregulation has been considered to be a key factor that affects aging and dementia. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a primary sensor of cellular energy states and regulates cellular energy metabolism...
February 2018: Experimental Neurobiology
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
Frank Matthes, Moritz M Hettich, Judith Schilling, Diana Flores-Dominguez, Nelli Blank, Thomas Wiglenda, Alexander Buntru, Hanna Wolf, Stephanie Weber, Ina Vorberg, Alina Dagane, Gunnar Dittmar, Erich Wanker, Dan Ehninger, Sybille Krauss
Alzheimer's disease (AD) is characterized by two neuropathological hallmarks: senile plaques, which are composed of amyloid-β (Aβ) peptides, and neurofibrillary tangles, which are composed of hyperphosphorylated tau protein. Aβ peptides are derived from sequential proteolytic cleavage of the amyloid precursor protein (APP). In this study, we identified a so far unknown mode of regulation of APP protein synthesis involving the MID1 protein complex: MID1 binds to and regulates the translation of APP mRNA...
December 2018: Cell Death Discovery
Julia Tschirka, Madlen Kreisor, Janina Betz, Dirk Grundemann
The candidate vitamin ergothioneine (ET) is a unique antioxidant. Expression of the ergothioneine transporter (ETT) (gene symbol SLC22A4) in distinct cells is thought to signal intracellular ET activity, since we have previously shown that the ETT is highly selective for ET. Unfortunately, some continue to hold the ETT as a relevant drug transporter, using the misleading functional name OCTN1, novel organic cation transporter. The present study was provoked by 2 recent reports in which new ETT substrates were declared...
March 12, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Robert Krysiak, Witold Szkróbka, Bogusław Okopień
BACKGROUND: Metformin was found to decrease serum levels of prolactin and thyrotropin. The aim of this study was to investigate the effect of this drug on hypothalamic-pituitary-ovarian axis activity in postmenopausal women with recently diagnosed and untreated glucose metabolism abnormalities. METHODS: The study included three matched groups of postmenopausal women: patients with type 2 diabetes (group A, n=16), women with prediabetes (group B, n=14), and individuals with normal glucose metabolism (group C, n=14)...
March 12, 2018: Experimental and Clinical Endocrinology & Diabetes
Helmuth Haslacher, Hannelore Fallmann, Claudia Waldhäusl, Edith Hartmann, Oswald F Wagner, Werner Waldhäusl
BACKGROUND: T1D treatment requires informed self-responsible patients, who, however, frequently miss their therapeutic goals, providing considerable potential for improvement. METHODS: This observational report evaluates T1D patients [N = 109], aged ≥18 years (range 22-82), poorly controlled at home, at and 3 weeks after their admission to our diabetes rehabilitation clinic [DRC], where they were offered standardized, but unmonitored life-style modification. RESULTS: At admission, patients displayed elevated HbA1c values (66 mmol/mol [57; 81]), a high prevalence of co-morbidities (88%), lipodystrophies due to monolocal insulin injections (42%), a low rate of influenza (16%) and pneumococcal (7%) immunization, and underuse of lipid-lowering drugs (-38%)...
2018: PloS One
Valerie Evans, Peter Roderick, Allyson M Pollock
There is growing national and international concern about the drug regulatory system in India. Parliamentary reports have highlighted the presence of high numbers of unapproved medicines and irrational combinations of both approved and unapproved drugs in the Indian market-place. Fixed-dose combinations (FDCs) are a peculiar feature of the Indian pharmaceutical landscape. Although metformin is a first-line treatment, FDCs for diabetes in India account for two-thirds of all diabetes medicine sales, and some have not been approved by the Central Drugs Standard Control Organization (CDSCO)...
2018: BMJ Global Health
Milton Packer
Although dipeptidyl peptidase (DPP)-4 inhibitors have been reported to have a neutral effect on thromboembolic vaso-occlusive events in large-scale trials, they act to potentiate several endogenous peptides that can exert deleterious cardiovascular effects. Experimentally, DPP-4 inhibitors may augment the ability of glucagon-like peptide-1 to stimulate cyclic adenosine monophosphate in cardiomyocytes, and potentiation of the effects of stromal cell-derived factor-1 by DPP-4 inhibitors may aggravate cardiac fibrosis...
March 1, 2018: JACC. Heart Failure
Xia Dai, Zu-Chun Luo, Lu Zhai, Wen-Piao Zhao, Feng Huang
INTRODUCTION: Empagliflozin is a new, emerging oral hypoglycemic agent (OHA) which has shown significant benefits in type 2 diabetes mellitus (T2DM) patients with cardiovascular disease. In this analysis, our aim was to systematically compare the adverse drug events (ADEs) associated with a low (10 mg) versus a high (25 mg) dose of empagliflozin as (1) monotherapy, (2) as an add-on to other OHAs, and (3) as an add-on specifically to metformin, in patients who were treated for T2DM. METHODS: This was a systematic review and meta-analysis of randomized controlled trials that compared empagliflozin 10 mg versus 25 mg in patients who were treated for T2DM and which reported adverse drug reactions as their clinical endpoints...
March 9, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
Quoc-Ky Truong, Xuan-Lan Mai, Jae-Yong Lee, Jongsook Rhee, Dinh Vinh, Jongki Hong, Kyeong Ho Kim
A simple, sensitive, and rapid assay based on hydrophilic interaction liquid chromatography (HILIC) with tandem mass spectrometry was developed and validated for the simultaneous determination of metformin and 13 other oral antihyperglycaemic drugs in human urine using metoprolol as an internal standard. A simple sample clean-up procedure using the "dilute and shoot" approach enabled fast and reliable analysis. Chromatographic separation was performed on a HILIC column using an elution gradient of mobile phase A, composed of 1 mM ammonium formate (pH 5), and mobile phase B, composed of acetonitrile, at a flow rate of 0...
March 9, 2018: Archives of Pharmacal Research
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
Sushant Shengule, Kalyani Kumbhare, Dada Patil, Sanjay Mishra, Kishori Apte, Bhushan Patwardhan
Nisha Amalaki (NA), formulation with Curcuma longa Linn (Turmeric, Haridra, Nisha in Sanskrit; Family: Zingiberaceae) and Phyllanthus emblica Linn (Indian gooseberry, Amlaki in Sanskrit; Family: Phyllanthaceae) which is described for various diseases including diabetes in ayurvedic texts and Nighantus. The aim of the present study was to assess the pharmacokinetic (PK) and pharmacodynamic (PD) interactions of chemically standardized NA and Curcuminoids (CE) with metformin (MET) in normal and diabetic animals...
March 5, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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