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Glucose toxicity

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https://www.readbyqxmd.com/read/29351480/mechanistically-different-effects-of-fat-and-sugar-on-insulin-resistance-hypertension-and-gut-microbiota-in-rats
#1
Sara Ramos-Romero, Mercè Hereu, Lidia Atienza, Josefina Casas, Olga Jáuregui, Susana Amézqueta, Gabriel Dasilva, Isabel Medina, Maria Rosa Nogués, Marta Romeu, Josep Lluís Torres
Insulin resistance (IR) and impaired glucose tolerance (IGT) are the first manifestations of diet-induced metabolic alterations leading to type-2 diabetes, while hypertension is the deadliest risk factor of cardiovascular disease. The roles of dietary fat and fructose in the development of IR, IGT and hypertension are controversial. We tested the long-term effects of an excess of fat or sucrose (fructose/glucose) on healthy male Wistar Kyoto (WKY) rats. Fat affects IR and IGT earlier than fructose through low-grade systemic inflammation evidenced by liver inflammatory infiltration, increased levels of plasma interleukin-6, prostaglandin E2 and reduced levels of protective short-chain fatty acids without triggering hypertension...
January 2, 2018: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29351081/characterization-of-phosphate-transporter-s-and-understanding-their-role-in-leishmania-donovani-parasite
#2
K J Sindhu, Amit Kumar Kureel, Sheetal Saini, Smita Kumari, Pankaj Verma, Ambak Kumar Rai
Inorganic phosphate (Pi) is shown to be involved in excretion of methylglyoxal (MG) in the promastigote form of Leishmania donovani parasite. Absence of Pi leads to its accumulation inside the parasite. Accumulation of MG is toxic to the parasite and utilizes glyoxylase as well as excretory pathways for its detoxification. In addition, Pi is also reported to regulate activities of ectoenzymes and energy metabolism (glucose to pyruvate) etc. Thus, it is known to cumulatively affect the growth of Leishmania parasite...
March 26, 2018: Acta Parasitologica
https://www.readbyqxmd.com/read/29349532/a-novel-approach-in-treatment-of-tuberculosis-by-targeting-drugs-to-infected-macrophages-using-biodegradable-nanoparticles
#3
REVIEW
Shivangi, Laxman S Meena
Mycobacterium tuberculosis, the causative agent of tuberculosis is now causing death of more than 10 million people. Because of the development of drug-resistant TB, drug delivery to the infected site through nanoparticle had been studied for long time. Nanoparticles indicate different sorts of association with the natural particles of the body. Nanoparticles can be used as controlled or specific drug delivery system. It can be through temporal controlled or can be distribution controlled. Glucose polymer-based nanoparticles might play an important role as drug delivery system in case of targeted drug delivery in the infected site of the body or in infected macrophages, as they are biodegradable so there should not be any side effects of these particles in the body and also they show very slow immune response...
January 19, 2018: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/29346507/activity-and-safety-of-afatinib-in-a-window-pre-operative-eortc-study-in-patients-with-squamous-cell-carcinoma-of-the-head-and-neck-scchn
#4
J P Machiels, P Bossi, J Menis, M Lia, C Fortpied, Y Liu, R Lhommel, M Lemort, S Schmitz, S Canevari, L De Cecco, M Guzzo, R Bianchi, P Quattrone, F Crippa, T Duprez, Y Lalami, M Quiriny, N de Saint Aubain, P M Clement, R Coropciuc, E Hauben, L F Licitra
Background: To investigate the activity and safety of afatinib in the pre-operative treatment of squamous cell carcinoma of the head and neck (SCCHN). Patients and methods: This study was an open-label, randomized, multicenter, phase II window of opportunity trial. Treatment-naïve SCCHN patients selected for primary curative surgery were randomized (5:1 ratio) to receive afatinib during 14 days (day -15 until day -1) before surgery (day 0) or no treatment. Tumor biopsies, 2-[fluorine-18]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), and magnetic resonance imaging (MRI) were performed at diagnosis and just before surgery...
January 15, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29343667/genotypic-effects-on-sugar-and-by-products-of-liquid-hydrolysates-and-on-saccharification-of-acid-insoluble-residues-of-from-wheat-straw
#5
Ryoko Ohno, Hiroshi Teramura, Chiaki Ogino, Akihiko Kondo, Shigeo Takumi
Wheat straw is one of the major attractive resources for low-cost raw materials for renewable energy, biofuels and biochemicals. However, like other sources of lignocellulosic biomass, straw is a heterogeneous material due to its mixed origin from different tissue and cell types. Here, to examine the genotypic effects on biorefinery usage of wheat straw, straw obtained from different wheat cultivars and experimental lines was pretreated with dilute acid. Significant differences between cultivars were observed in the concentrations of glucose and toxic by-products of the liquid hydrolysates...
January 17, 2018: Genes & Genetic Systems
https://www.readbyqxmd.com/read/29339464/propionate-enters-gabaergic-neurons-inhibits-gaba-transaminase-causes-gaba-accumulation-and-lethargy-in-a-model-of-propionic-acidemia
#6
Cecilie Morland, Anne-Sofie Frøland, Mi Nyguyen Pettersen, Jon Storm-Mathisen, Vidar Gundersen, Frode Rise, Bjørnar Hassel
Propionic acidemia is the accumulation of propionate in blood due to dysfunction of propionyl-CoA carboxylase. The condition causes lethargy and striatal degeneration with motor impairment in humans. How propionate exerts its toxic effect is unclear. Here we show that intravenous administration of propionate causes dose-dependent propionate accumulation in the brain and transient lethargy in mice. Propionate, an inhibitor of histone deacetylase, entered GABAergic neurons, as could be seen from increased neuronal histone H4 acetylation in striatum and neocortex...
January 16, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/29338381/effect-of-the-diabetic-state-on-islet-engraftment-and-function-in-a-large-animal-model-of-islet-kidney-transplantation
#7
Prashanth Vallabhajosyula, Atsushi Hirakata, Matthew Weiss, Adam Griesemer, Akira Shimizu, Hanzhou Hong, Andreas Habertheuer, Vaja Tchipashvili, Kazuhiko Yamada, David H Sachs
In islet transplantation, in addition to immunologic and ischemic factors, the diabetic/hyperglycemic state of the recipient has been proposed, although not yet validated, as a possible cause of islet toxicity, contributing to islet loss during the engraftment period. Using a miniature swine model of islet transplantation, we have now assessed the effect of a persistent state of hyperglycemia on islet engraftment and subsequent function. An islet-kidney (IK) model previously described by our laboratory was utilized...
November 2017: Cell Transplantation
https://www.readbyqxmd.com/read/29337308/rage-binds-preamyloid-iapp-intermediates-and-mediates-pancreatic-%C3%AE-cell-proteotoxicity
#8
Andisheh Abedini, Ping Cao, Annette Plesner, Jinghua Zhang, Meilun He, Julia Derk, Sachi A Patil, Rosa Rosario, Jacqueline Lonier, Fei Song, Hyunwook Koh, Huilin Li, Daniel P Raleigh, Ann Marie Schmidt
Islet amyloidosis is characterized by the aberrant accumulation of islet amyloid polypeptide (IAPP) in pancreatic islets, resulting in β cell toxicity, which exacerbates type 2 diabetes and islet transplant failure. It is not fully clear how IAPP induces cellular stress or how IAPP-induced toxicity can be prevented or treated. We recently defined the properties of toxic IAPP species. Here, we have identified a receptor-mediated mechanism of islet amyloidosis-induced proteotoxicity. In human diabetic pancreas and in cellular and mouse models of islet amyloidosis, increased expression of the receptor for advanced glycation endproducts (RAGE) correlated with human IAPP-induced (h-IAPP-induced) β cell and islet inflammation, toxicity, and apoptosis...
January 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29336990/failure-of-intracardiac-pacing-after-fatal-propafenone-overdose-a-case-report
#9
Ivan Zeljković, Nikola Bulj, Matea Kolačević, Vedran Čabrilo, Diana Delić Brkljačić, Šime Manola
BACKGROUND: Propafenone is a sodium-channel blocker, class IC antiarrhythmic drug, frequently used to manage supraventricular dysrhythmias, especially atrial fibrillation. We report a self mono-intoxication with propafenone. CASE REPORT: A 68-year-old woman presented with a decreased level of consciousness, hypotension, and electrocardiogram showing QRS widening with atrial asystole and extreme bradycardia < 20 beats/min. After initial stabilization with transcutaneous pacing, laboratory findings detected normal electrolyte ranges and metabolic acidosis, and her medical history revealed availability of propafenone due to paroxysmal atrial fibrillation and depressive syndrome, which led to the suspicion of intoxication...
January 11, 2018: Journal of Emergency Medicine
https://www.readbyqxmd.com/read/29336483/glucose-metabolism-during-in-vitro-maturation-of-mouse-oocytes-an-study-using-rna-interference
#10
Hong-Li Xie, Shuai Zhu, Jie Zhang, Jing Wen, Hong-Jie Yuan, Liu-Zhu Pan, Ming-Jiu Luo, Jing-He Tan
In previous studies on glucose metabolism during in vitro maturation, intact cumulus-oocyte complexes (COCs) were treated with enzyme inhibitors/activators. Because inhibitors/activators may have non-specificity and/or toxicity, and culture of COCs cannot differentiate whether glucose metabolism of cumulus cells (CCs) or that of the oocyte supports oocyte maturation, results from the previous studies must be verified by silencing genes in either CCs or cumulus-denuded oocytes (DOs). In this study, RNAi was adopted to specify the effects of glucose metabolism in CCs or DOs on oocyte maturation...
January 16, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29335813/organic-acidurias-in-adults-late-complications-and-management
#11
Ali Tunç Tuncel, Nikolas Boy, Marina A Morath, Friederike Hörster, Ulrike Mütze, Stefan Kölker
Organic acidurias (synonym, organic acid disorders, OADs) are a heterogenous group of inherited metabolic diseases delineated with the implementation of gas chromatography/mass spectrometry in metabolic laboratories starting in the 1960s and 1970s. Biochemically, OADs are characterized by accumulation of mono-, di- and/or tricarboxylic acids ("organic acids") and corresponding coenzyme A, carnitine and/or glycine esters, some of which are considered toxic at high concentrations. Clinically, disease onset is variable, however, affected individuals may already present during the newborn period with life-threatening acute metabolic crises and acute multi-organ failure...
January 15, 2018: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/29335619/cytokine-mif-enhances-blood-brain-barrier-permeability-impact-for-therapy-in-ischemic-stroke
#12
Yu-Chuan Liu, Yung-Hsu Tsai, Sung-Chun Tang, Houng-Chi Liou, Kai-Hsiang Kang, Horng-Huei Liou, Jiann-Shing Jeng, Wen-Mei Fu
Ischemic stroke is a devastating disease with limited therapeutic options. It is very urgent to find a new target for drug development. Here we found that the blood level of MIF in ischemic stroke patients is upregulated. To figure out the pathological role of MIF in ischemic stroke, both in vitro and in vivo studies were conducted. For in vitro studies, primary cortical neuron cultures and adult rat brain endothelial cells (ARBECs) were subjected to oxygen-glucose deprivation (OGD)/reoxygenation. Middle cerebral artery occlusion (MCAo) rodent models were used for in vivo studies...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29333038/antihyperglycemic-potential-of-saponin-enriched-fraction-from-pithecellobium-dulce-benth-seed-extract
#13
Mahesh Kumar, Jeyabalan Govindrajan, Narendra Kumar Nyola
Background: Indian traditional system of medicine uses Pithecellobium dulce for the treatment of diabetes mellitus. Objectives: This study aims to develop an extract rich in saponins derived from seeds of the plant and to evaluate its antihyperglycemic potential in vitro and in vivo. Materials and Methods: Defatted seeds were extracted with methanol and processed to afford saponin-enriched fraction (Pithecellobium dulce saponin-enriched fraction [PDSEF])...
December 2017: Pharmacognosy Research
https://www.readbyqxmd.com/read/29330151/interleukin-22-reverses-human-islet-dysfunction-and-apoptosis-triggered-by-hyperglycemia-and-light
#14
Shadab Abadpour, Bente Halvorsen, Afaf Sahraoui, Olle Korsgren, Pål Aukrust, Hanne Scholz
Interleukin (IL)-22 has recently been suggested as an anti-inflammatory cytokine that could protect the islet cells from inflammation- and glucose-induced toxicity. We have previously shown that the tumor necrosis factor family member, LIGHT can impair human islet function at least partly via pro-apoptotic effects. Herein, we aimed to investigate the protective role of IL-22 on human islets exposed to the combination of hyperglycemia and LIGHT. First, we found up-regulation of LIGHT receptors (LTβR and HVEM) in engrafted human islets exposed to hyperglycemia (>11 mM) for 17 days post transplantation by using a double islet transplantation mouse model as well as in human islets cultured with high glucose (HG) (20mM glucose) + LIGHT in vitro and this latter effect was attenuated by IL-22...
January 12, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29325602/bile-acid-metabolism-in-liver-pathobiology
#15
John Y L Chiang, Jessica M Ferrell
Bile acids facilitate intestinal nutrient absorption and biliary cholesterol secretion to maintain bile acid homeostasis, which is essential for protecting liver and other tissues and cells from cholesterol and bile acid toxicity. Bile acid metabolism is tightly regulated by bile acid synthesis in the liver and bile acid biotransformation in the intestine. Bile acids are endogenous ligands that activate a complex network of nuclear receptor farnesoid X receptor and membrane G protein-coupled bile acid receptor-1 to regulate hepatic lipid and glucose metabolic homeostasis and energy metabolism...
January 11, 2018: Gene Expression
https://www.readbyqxmd.com/read/29324279/inhibition-of-udp-glucose-dehydrogenase-by-6-thiopurine-and-its-oxidative-metabolites-possible-mechanism-for-its-interaction-within-the-bilirubin-excretion-pathway-and-6tp-associated-liver-toxicity
#16
Chamitha J Weeramange, Cassie M Binns, Chixiang Chen, Ryan J Rafferty
6-Thiopurine (6TP) is an actively prescribed drug in the treatment of various diseases ranging from Crohn's disease and other inflammatory diseases to acute lymphocytic leukemia and non-Hodgkin's leukemia. While 6TP has beneficial therapeutic uses, severe toxicities are also reported with its use, such as jaundice and liver toxicity. While numerous investigations into the mode in which toxicity originates has been undertaken. None have investigated the effects of inhibition towards UDP-Glucose Dehydrogenase (UDPGDH), an oxidative enzyme responsible for UDP-glucuronic acid (UDPGA) formation or UDP-Glucuronosyl transferase (UGT1A1), which is responsible for the conjugation of bilirubin with UDPGA for excretion...
December 30, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29322369/proteomic-and-metabolomic-analysis-of-marine-medaka-oryzias-melastigma-after-acute-ammonia-exposure
#17
Limei Zhu, Na Gao, Ruifang Wang, Li Zhang
Ammonia is both a highly toxic environmental pollutant and the major nitrogenous waste produced by ammoniotelic teleosts. Although the acute toxic effects of ammonia have been widely studied in fish, the biochemical mechanisms of its toxicity have not been understood comprehensively. In this study, we performed comparative proteomic and metabolomic analysis between ammonia-challenged (1.2 and 2.6 mmol L-1 NH4Cl for 96 h) and control groups of marine medaka (Oryzias melastigma) to identify changes of the metabolite and protein profiles in response to ammonia stress...
January 10, 2018: Ecotoxicology
https://www.readbyqxmd.com/read/29322248/a-reversible-liquid-drop-aggregation-controls-glucose-response-in-yeast
#18
REVIEW
Kobi Simpson-Lavy, Martin Kupiec
Glucose is the preferred carbon of the yeast Saccharomyces cerevisiae. Depletion of glucose activates SNF1 (yeast AMP-activated protein kinase-AMPK), allowing cells to switch from fermentation to respiration. We have recently characterized the mechanism by which SNF1 activity is regulated by the Std1 protein, and its regulator Sip5. The hitherto uncharacterized protein kinase Vhs1 phosphorylates Sip5 in response to glucose availability, disengaging it from Std1 and promoting the sequestering of the SNF1 activator out of the nucleus into cytoplasmic puncta...
January 10, 2018: Current Genetics
https://www.readbyqxmd.com/read/29320490/the-glutamine-synthetase-of-trypanosoma-cruzi-is-required-for-its-resistance-to-ammonium-accumulation-and-evasion-of-the-parasitophorous-vacuole-during-host-cell-infection
#19
Marcell Crispim, Flávia Silva Damasceno, Agustín Hernández, María Julia Barisón, Ismael Pretto Sauter, Raphael Souza Pavani, Alexandre Santos Moura, Elizabeth Mieko Furusho Pral, Mauro Cortez, Maria Carolina Elias, Ariel Mariano Silber
Trypanosoma cruzi, the etiological agent of Chagas disease, consumes glucose and amino acids depending on the environmental availability of each nutrient during its complex life cycle. For example, amino acids are the major energy and carbon sources in the intracellular stages of the T. cruzi parasite, but their consumption produces an accumulation of NH4+ in the environment, which is toxic. These parasites do not have a functional urea cycle to secrete excess nitrogen as low-toxicity waste. Glutamine synthetase (GS) plays a central role in regulating the carbon/nitrogen balance in the metabolism of most living organisms...
January 10, 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29319508/genes-controlling-2-deoxyglucose-induced-lysis-and-formation-of-reactive-oxygen-species-in-schizosaccharomyces-pombe
#20
Akshay Vishwanatha, Cletus J M D'Souza, Martin E Schweingruber
Schizosaccharomyces pombe cells of strains each carrying a deletion of one of the genes snf5, ypa1, pho7 and pas1 and of a strain overexpressing gene odr1, have been previously shown to grow in presence of the toxic glucose analogue 2-deoxyglucose (2-DG). Here we report that these genes control 2-DG induced lysis and are, with the exception of odr1, also involved in control of formation of reactive oxygen species (ROS) upon exposure of cells to H2O2. Lysis of deletion strains, but not of strain overexpressing odr1, is dependent on glucose concentration of the medium whereas ROS formation is glucose independent...
September 27, 2017: Polish Journal of Microbiology
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