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Glucose transporter deficiency

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https://www.readbyqxmd.com/read/28822962/glucose-transporter-4-glut4-deficient-hearts-develop-maladaptive-hypertrophy-in-response-to-physiologic-or-pathologic-stresses
#1
Adam Raymond Wende, Jaetaek Kim, William Holland, Benjamin E Wayment, Brian T O'Neill, Joseph Tuinei, Manoja K Brahma, Mark E Pepin, Mark A McCrory, Ivan Luptak, Ganesh V Halade, Sheldon E Litwin, E Dale Abel
Pathological cardiac hypertrophy may be associated with reduced expression of the GLUT4 glucose transporter in contrast to exercise-induced cardiac hypertrophy, where GLUT4 levels are increased. However, mice with cardiac specific deletion of GLUT4 (G4H-/-) have normal cardiac function in the unstressed state. This study tested the hypothesis that cardiac GLUT4 is required for myocardial adaptations to hemodynamic demands. G4H-/- and control littermates (Con) were subjected to either a pathological model of left ventricular pressure overload (transverse aortic constriction; TAC) or a physiological model of endurance exercise (swim training)...
August 19, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28807879/apigenin-induced-abcc1-mediated-efflux-of-glutathione-from-mature-erythrocytes-inhibits-the-proliferation-of-plasmodium-falciparum
#2
Ohud Fallatah, Elias Georges
Plasmodium falciparum infection of mature normal erythrocytes leads to heightened oxidative stress that is tolerated in normal but not in erythrocytes from sickle-cell, β-thalassemia, and glucose-6-phosphate dehydrogenase (G6PD) deficiency hosts. In this report, it was of interest to perturb the redox homeostasis of normal erythrocytes through drug-induced active efflux of glutathione via erythrocyte ABCC1 (member of the C- subfamily of the human ATP-binding cassette (ABC) transporters). To achieve this objective, we made use of apigenin, shown previously to activate ABCC1 glutathione efflux in mature erythrocytes...
August 11, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28799513/ketogenic-diets-in-the-treatment-of-epilepsy
#3
Maurizio Elia, Joerg Klepper, Baerbel Leiendecker, Hans Hartmann
BACKGROUND: Although a larger number of antiepileptic drugs became available in the last decades, epilepsy remains drug-resistant in approximately a third of patients. Ketogenic diet (KD), first proposed at the beginning of the last century, is complex and has anticonvulsant effects, yet not completely understood. Over the last decades, different types of ketogenic diets (KDs) have been developed, namely classical KD and modified Atkins diet (MAD). They offer an effective alternative for children and adults with drug-resistant epilepsies...
August 9, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28798690/risk-of-myopathy-in-patients-in-therapy-with-statins-identification-of-biological-markers-in-a-pilot-study
#4
Giulia M Camerino, Olimpia Musumeci, Elena Conte, Kejla Musaraj, Adriano Fonzino, Emanuele Barca, Marco Marino, Carmelo Rodolico, Domenico Tricarico, Claudia Camerino, Maria R Carratù, Jean-François Desaphy, Annamaria De Luca, Antonio Toscano, Sabata Pierno
Statin therapy may induce skeletal muscle damage ranging from myalgia to severe rhabdomyolysis. Our previous preclinical studies showed that statin treatment in rats involves the reduction of skeletal muscle ClC-1 chloride channel expression and related chloride conductance (gCl). An increase of the activity of protein kinase C theta (PKC theta) isoform, able to inactivate ClC-1, may contribute to destabilize sarcolemma excitability. These effects can be detrimental for muscle function leading to drug-induced myopathy...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28798491/phytochromobilin-deficiency-impairs-sugar-metabolism-through-the-regulation-of-cytokinin-and-auxin-signaling-in-tomato-fruits
#5
Ricardo Ernesto Bianchetti, Aline Bertinatto Cruz, Bruna Soares Oliveira, Diego Demarco, Eduardo Purgatto, Lázaro Eustáquio Pereira Peres, Magdalena Rossi, Luciano Freschi
Phytochomes and plant hormones have been emerging as important regulators of fleshy fruit biology and quality traits; however, the relevance of phytochrome-hormonal signaling crosstalk in controlling fruit development and metabolism remains elusive. Here, we show that the deficiency in phytochrome chromophore phytochromobilin (PΦB) biosynthesis inhibits sugar accumulation in tomato (Solanum lycopersicum) fruits by transcriptionally downregulating sink- and starch biosynthesis-related enzymes, such as cell-wall invertases, sucrose transporters and ADP-glucose pyrophosphorylases...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28794109/comparative-study-on-glucose-transporters-expression-and-activity-between-stem-cell-derived-brain-microvascular-endothelial-cells-and-hcmec-d3-cells
#6
Abraham J Al-Alahmad
Glucose constitutes the major source of energy of mammalian brains. Glucose uptake at the blood-brain barrier (BBB) occurs through a facilitated glucose transport, through glucose transporter 1 (GLUT1), although other isoforms have been described at the BBB. Mutations in GLUT1 is associated with the GLUT1 deficiency syndrome (GLUT1DS), yet none of the current in vitro models of the human BBB maybe suited for modelling such disorder. In this study, we investigated the expression of glucose transporters and glucose diffusion across the human BBB using brain microvascular endothelial cells (BMECs) derived from healthy patient-derived induced pluripotent stem cells (iPSCs)...
August 9, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28791698/increased-systemic-exposure-and-stronger-cardiovascular-and-metabolic-adverse-reactions-to-fenoterol-in-individuals-with-heritable-oct1-deficiency
#7
Mladen V Tzvetkov, Johannes Matthaei, Sherin Pojar, Frank Faltraco, Sabrina Vogler, Thomas Prukop, Tina Seitz, Jürgen Brockmöller
Fenoterol is widely used anti-asthmatic and tocolytic agent, but high plasma concentrations of fenoterol may lead to severe and even fatal adverse reactions. We studied whether heritable deficiency of the liver organic cation transporter OCT1, a trait observed in 3% of Europeans and White Americans, affects fenoterol plasma concentrations and toxicity. OCT1 transported fenoterol with high affinity. OCT1 inhibition in human hepatocytes reduced fenoterol uptake 3-fold. After administration of 180 µg fenoterol to 39 healthy individuals, the OCT1-deficicient individuals (zero active OCT1 alleles, n=5) showed 1...
August 9, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28768837/vitamin-d-in-the-spectrum-of-prediabetes-and-cardiovascular-autonomic-dysfunction
#8
REVIEW
Rumyana Dimova, Tsvetalina Tankova, Nevena Chakarova
Vitamin D is a fat-soluble secosteroid hormone with pleiotropic effects. 1,25-Dihydroxyvitamin D coordinates the biosynthesis of neurotransmitters in the central nervous system, which regulate cardiovascular autonomic function and may explain its putative role in the development of cardiovascular autonomic neuropathy (CAN). CAN is an independent risk factor for mortality in patients with diabetes and prediabetes and is associated with an increased risk of developing type 2 diabetes and cardiovascular disease...
August 2, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28751004/polyphenols-activate-energy-sensing-network-in-insulin-resistant-models
#9
Radika Mutlur Krishnamoorthy, Anuradha Carani Venkatraman
Unhealthy diet deficient in fruits and vegetables but rich in calories is considered to be one factor responsible for the increased prevalence of insulin resistance and type 2 diabetes (T2D). The consumption of fast foods and soft drinks increases fructose consumption per se and this is of major concern since prolonged fructose intake induces insulin resistance and thereby T2D. The energy homeostasis is regulated by a network consisting of "fuel gauze" called AMP-activated protein kinase (AMPK), the NAD(+) dependent type III deacetylase (SIRT1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) which is disrupted in T2D...
July 24, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28740135/establishing-a-yeast-based-screening-system-for-discovery-of-human-glut5-inhibitors-and-activators
#10
Joanna Tripp, Christine Essl, Cristina V Iancu, Eckhard Boles, Jun-Yong Choe, Mislav Oreb
Human GLUT5 is a fructose-specific transporter in the glucose transporter family (GLUT, SLC2 gene family). Its substrate-specificity and tissue-specific expression make it a promising target for treatment of diabetes, metabolic syndrome and cancer, but few GLUT5 inhibitors are known. To identify and characterize potential GLUT5 ligands, we developed a whole-cell system based on a yeast strain deficient in fructose uptake, in which GLUT5 transport activity is associated with cell growth in fructose-based media or assayed by fructose uptake in whole cells...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28736440/repin1-deficiency-in-adipose-tissue-improves-whole-body-insulin-sensitivity-and-lipid-metabolism
#11
N Hesselbarth, A Kunath, M Kern, M Gericke, N Mejhert, M Rydén, M Stumvoll, M Blüher, N Klöting
BACKGROUND/OBJECTIVES: Replication initiator 1 (Repin1) gene encodes for a zinc-finger protein and has been implicated in the regulation of adipocyte cell size and glucose transport in vitro. Here, we investigate the consequences of reduced adipose tissue (AT) Repin1 expression in vivo. SUBJECTS/METHODS: We have inactivated the Repin1 gene in adipose tissue (iARep(-/-)) at an age of four weeks using tamoxifen-inducible gene targeting strategies on the background of C57BL/6NTac mice...
July 24, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28734787/selenium-deficiency-induced-thioredoxin-suppression-and-thioredoxin-knock-down-disbalanced-insulin-responsiveness-in-chicken-cardiomyocytes-through-pi3k-akt-pathway-inhibition
#12
Jie Yang, Sattar Hamid, Jingzeng Cai, Qi Liu, Shiwen Xu, Ziwei Zhang
Thioredoxin (Txn) system is the most crucial antioxidant defense mechanism in cell consisting of Txn, thioredoxin reductase (TR) and Nicotinamide Adenine Dinucleotide Phosphate (NADPH). Perturbations in Txn system may compromise cell survival through oxidative stress induction. Metabolic activity of insulin plays important roles in fulfilling the stable and persistent demands of heart through glucose metabolism. However, the roles of Txn and Txn system in insulin modulated cardiac energy metabolism have been less reported...
July 19, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28688166/triheptanoin-for-the-treatment-of-brain-energy-deficit-a-14-year-experience
#13
REVIEW
Fanny Mochel
Triheptanoin is an odd-chain triglyceride with anaplerotic properties-that is, replenishing the pool of metabolic intermediates in the Krebs cycle. Unlike even-chain fatty acids metabolized to acetyl-CoA only, triheptanoin can indeed provide both acetyl-CoA and propionyl-CoA, two key carbon sources for the Krebs cycle. Triheptanoin was initially used in patients with long-chain fatty acid oxidation disorders. The first demonstration of the possible benefit of triheptanoin for brain energy deficit came from a patient with pyruvate carboxylase deficiency, a severe metabolic disease that affects anaplerosis in the brain...
July 8, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28687021/insulin-resistance-in-vitamin-d-deficient-mice-is-alleviated-by-n-acetylcysteine
#14
Zhao-Hui Cui, Qi Yuan, Li Mao, Feng-Li Chen, Feng Ji, Sha Tao
Vitamin D deficiency will lead to insulin resistance. In the current study, vitamin D3 1α-Hydroxylase ["1α(OH)ase"] knockout mice were generated to mimic vitamin D deficiency in vivo. As compared to the wild-type mice, the liver tissues of the knockout mice showed impaired insulin signaling, decreased glucose transporter 4 expression and increased reactive oxygen species production. Meanwhile, p53-p21 activation, apoptosis intensity and pro-inflammatory cytokines (IL-6, IL-1 and MIP-1α) level were significantly increased in the knockout mice livers...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28687018/vitamin-d-deficiency-causes-insulin-resistance-by-provoking-oxidative-stress-in-hepatocytes
#15
Sha Tao, Qi Yuan, Li Mao, Feng-Li Chen, Feng Ji, Zhao-Hui Cui
Vitamin D deficiency could cause insulin resistance. However, the underlying mechanisms are unclear. The 1α-Hydroxylase ["1α(OH)ase"] is a key enzyme for activate vitamin D3 synthesis. Here, we show that 1α(OH)ase stable knockdown by targeted shRNA led to vitamin D3 depletion in L02 hepatocytes. 1α(OH)ase silence also inhibited insulin-induced downstream signaling (IRS-1, ERK and AKT) transduction and glucose transporter 4 expression. Further, 1α(OH)ase shRNA in L02 hepatocytes led to significant reactive oxygen species production, p53-p21 activation and DNA damages...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28674555/a-design-build-test-cycle-using-modeling-and-experiments-reveals-interdependencies-between-upper-glycolysis-and-xylose-uptake-in-recombinant-s-cerevisiae-and-improves-predictive-capabilities-of-large-scale-kinetic-models
#16
Ljubisa Miskovic, Susanne Alff-Tuomala, Keng Cher Soh, Dorothee Barth, Laura Salusjärvi, Juha-Pekka Pitkänen, Laura Ruohonen, Merja Penttilä, Vassily Hatzimanikatis
BACKGROUND: Recent advancements in omics measurement technologies have led to an ever-increasing amount of available experimental data that necessitate systems-oriented methodologies for efficient and systematic integration of data into consistent large-scale kinetic models. These models can help us to uncover new insights into cellular physiology and also to assist in the rational design of bioreactor or fermentation processes. Optimization and Risk Analysis of Complex Living Entities (ORACLE) framework for the construction of large-scale kinetic models can be used as guidance for formulating alternative metabolic engineering strategies...
2017: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/28673577/cognitive-impairment-in-diabetes-and-poor-glucose-utilization-in-the-intracellular-neural-milieu
#17
Carlos M Contreras, Ana G Gutiérrez-García
The main characteristic of diabetes is hyperglycemia. Depending on whether diabetes is type-1 or type-2, it is characterized by deficiencies in insulin secretion, insulin receptor sensitivity, hexokinase activity, and glucose transport. Current drug treatments are able to lower circulating glucose but do not address the problem of glucose utilization in the intracellular milieu, the consequence of which is tissue damage. In the long-term, such changes can produce structural damage in many cortical and subcortical brain areas that are related to cognitive function...
July 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28666985/keratins-regulate-%C3%AE-cell-mitochondrial-morphology-motility-and-homeostasis
#18
Jonas S G Silvander, Sofie M Kvarnström, Angeli Kumari-Ilieva, Anup Shrestha, Catharina M Alam, Diana M Toivola
Loss of the epithelial intermediate filament protein keratin 8 (K8) in murine β-cells leads to irregular insulin vesicles and decreased insulin levels. Because mitochondria are central in glucose-stimulated insulin secretion, the relationship between keratins and β-cell mitochondrial function and morphology was investigated. β-cells in murine K8 knockout (K8(-/-)) islets of Langerhans have increased numbers of mitochondria, which are rounder and have diffuse cristae, as seen by electron microscopy. The mitochondrial network in primary cultured K8(-/-) β-cells is more fragmented compared with K8(+/+) mitochondria, correlating with decreased levels of mitofusin 2 and the mitofusin 2- and keratin-binding protein trichoplein...
June 30, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28653367/significance-of-l-carnitine-for-human-health
#19
REVIEW
María M Adeva-Andany, Isabel Calvo-Castro, Carlos Fernández-Fernández, Cristóbal Donapetry-García, Ana María Pedre-Piñeiro
Carnitine acyltransferases catalyze the reversible transfer of acyl groups from acyl-coenzyme A esters to l-carnitine, forming acyl-carnitine esters that may be transported across cell membranes. l-Carnitine is a wáter-soluble compound that humans may obtain both by food ingestion and endogenous synthesis from trimethyl-lysine. Most l-carnitine is intracellular, being present predominantly in liver, skeletal muscle, heart and kidney. The organic cation transporter-2 facilitates l-carnitine uptake inside cells...
August 2017: IUBMB Life
https://www.readbyqxmd.com/read/28639913/novel-roles-of-folic-acid-as-redox-regulator-modulation-of-reactive-oxygen-species-sinker-protein-expression-and-maintenance-of-mitochondrial-redox-homeostasis-on-hepatocellular-carcinoma
#20
Kun-Goung Lai, Chi-Fen Chen, Chun-Te Ho, Jun-Jen Liu, Tsan-Zon Liu, Chi-Liang Chern
We provide herein several lines of evidence to substantiate that folic acid (or folate) is a micronutrient capable of functioning as a novel redox regulator on hepatocellular carcinoma. First, we uncovered that folate deficiency could profoundly downregulate two prominent anti-apoptotic effectors including survivin and glucose-regulated protein-78. Silencing of either survivin or glucose-regulated protein-78 via small interfering RNA interfering technique established that both effectors could serve as reactive oxygen species sinker proteins...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
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