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Glucose transporter deficiency

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https://www.readbyqxmd.com/read/28090774/biakamides-a-d-unique-polyketides-from-a-marine-sponge-act-as-selective-growth-inhibitors-of-tumor-cells-adapted-to-nutrient-starvation
#1
Naoyuki Kotoku, Ryosuke Ishida, Hirokazu Matsumoto, Masayoshi Arai, Kazunari Toda, Andi Setiawan, Osamu Muraoka, Motomasa Kobayashi
Biakamides A-D, novel unusually unique polyketides, were isolated from an Indonesian marine sponge (Petrosaspongia sp.) with a constructed bioassay using PANC-1 human pancreatic cancer cells. Through detailed analyses of the one- and two-dimensional nuclear magnetic resonance (NMR) spectra of biakamides, planar chemical structures possessing a terminal thiazole, two N-methyl amides, a chloromethylene, and a substituted butyryl moiety were obtained. After elucidation of the configuration of the secondary alcohol moiety in biakamides A and B, the absolute stereostructures of the two secondary methyl groups in biakamides A-D were determined by the asymmetric total syntheses of all possible stereoisomers from the optically pure monoprotected 2,4-dimethyl-1,5-diol...
January 16, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28070879/a-review-of-pharmacogenetics-of-antimalarials-and-associated-clinical-implications
#2
REVIEW
Hazem Elewa, Kyle John Wilby
Genetic variability in drug-metabolizing enzymes and drug transporters is known to influence the pharmacokinetics of many drugs. Antimalarial drugs are a class of agents known to utilize metabolic and elimination pathways prone to genetic variation. This paper aims to review the genetic variants affecting antimalarial medications and discuss their clinical implications. Data were identified for the genes coding for the cytochrome P450 (CYP) enzymes: CYP2C8, CYP2C19, CYP2A6, CYP2D6, CYP2B6, and the P-glycoprotein drug transporter...
January 9, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28070695/barth-syndrome-connecting-cardiolipin-to-cardiomyopathy
#3
REVIEW
Nikita Ikon, Robert O Ryan
The Barth syndrome (BTHS) is caused by an inborn error of metabolism that manifests characteristic phenotypic features including altered mitochondrial membrane phospholipids, lactic acidosis, organic acid-uria, skeletal muscle weakness and cardiomyopathy. The underlying cause of BTHS has been definitively traced to mutations in the tafazzin (TAZ) gene locus on chromosome X. TAZ encodes a phospholipid transacylase that promotes cardiolipin acyl chain remodeling. Absence of tafazzin activity results in cardiolipin molecular species heterogeneity, increased levels of monolysocardiolipin and lower cardiolipin abundance...
January 9, 2017: Lipids
https://www.readbyqxmd.com/read/28068143/adaptations-to-excess-choline-in-insulin-resistant-and-pcyt2-deficient-skeletal-muscle
#4
Adrian Taylor, Laila Cigana Schenkel, Maiya Yokich, Marica Bakovic
It was hypothesized that choline supplementation in insulin resistant (IR) CTP:phosphoethanolamine cytidylyltransferase deficient (Pcyt2(+/-)) mice would ameliorate muscle function by remodeling glucose and fatty acid (FA) metabolism. Pcyt2(+/-) mice either received no treatment or were allowed access to 2 mg/mL choline in drinking water for 4 weeks. Skeletal muscle was harvested from choline treated and untreated mice. Lipid analysis and metabolic gene expression and signaling pathways were compared between untreated Pcyt2(+/-) mice, treated Pcyt2(+/-) mice, and Pcyt2(+/+) mice...
September 6, 2016: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28056409/efficacy-of-metformin-in-human-single-hair-fibre-by-atr-ftir-spectroscopy-coupled-with-statistical-analysis
#5
Kamatchi Sundaramoorthi, Gunasekaran Sethu, Sailatha Ethirajulu, Pavithra Raja Marthandam
Diabetes mellitus is chronic metabolic disorder, resulting from insulin deficiency, characterized by hyperglycemia altered metabolism of carbohydrates, proteins and lipids and an increased risk of vascular complications. There are different classes of anti-diabetic drugs in allopathic system of medicine. Metformin (dimethyl biguanide) is a blood glucose lowering agent used in the treatment of non-insulin dependent diabetes mellitus. Almost in all diseases the blood serves as the primary metabolic transport system in the body...
December 27, 2016: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28040509/integration-of-proteomics-and-metabolomics-to-elucidate-metabolic-adaptation-in-leishmania
#6
Snezhana Akpunarlieva, Stefan Weidt, Dhilia Lamasudin, Christina Naula, David Henderson, Michael Barrett, Karl Burgess, Richard Burchmore
: Leishmania parasites multiply and develop in the gut of a sand fly vector in order to be transmitted to a vertebrate host. During this process they encounter and exploit various nutrients, including sugars, and amino and fatty acids. We have previously generated a mutant Leishmania line that is deficient in glucose transport and which displays some biologically important phenotypic changes such as reduced growth in axenic culture, reduced biosynthesis of hexose-containing virulence factors, increased sensitivity to oxidative stress, and dramatically reduced parasite burden in both insect vector and macrophage host cells...
December 28, 2016: Journal of Proteomics
https://www.readbyqxmd.com/read/28018440/glucose-transport-1-deficiency-presenting-as-infantile-spasms-with-a-mutation-identified-in-exon-9-of-slc2a1
#7
Hyun Hee Lee, Yun Jung Hur
Glucose transport 1 (GLUT-1) deficiency is a rare syndrome caused by mutations in the glucose transporter 1 gene (SLC2A1) and is characterized by early-onset intractable epilepsy, delayed development, and movement disorder. De novo mutations and several hot spots in N34, G91, R126, R153, and R333 of exons 2, 3, 4, and 8 of SLC2A1 are associated with this condition. Seizures, one of the main clinical features of GLUT-1 deficiency, usually develop during infancy. Most patients experience brief and subtle myoclonic jerk and focal seizures that evolve into a mixture of different types of seizures, such as generalized tonic-clonic, absence, myoclonic, and complex partial seizures...
November 2016: Korean Journal of Pediatrics
https://www.readbyqxmd.com/read/28008588/losartan-improves-palmitate-induced-insulin-resistance-in-3t3-l1-adipocytes-through-upregulation-of-src-phosphorylation
#8
X Tian, M Ye, Y Cao, C Wang
Angiotensin II type 1 receptor blocker losartan has shown strongly anti-insulin resistance properties in vivo and in vitro; however, the underlying mechanisms are poorly understood. In this study, we demonstrate that losartan administration increased phosphorylation of Akt and its downstream Akt substrate of 160 kDa (AS160), enhanced plasma membrane translocation of glucose transporter type 4 (GLUT4), and increased glucose uptake, along with increased Src phosphorylation as well as reduced expression of docking protein 1(DOK1) in palmitate-treated 3T3-L1 adipocytes...
December 22, 2016: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28000448/glycoconjugated-site-selective-dna-methylating-agent-targeting-glucose-transporters-on-glioma-cells
#9
Mairin K Buchanan, Chase N Needham, Nina E Neill, Maria C White, Charles B Kelly, Kelly Mastro-Kishton, Lacie M Chauvigne-Hines, Tyler J Goodwin, Andrew L McIver, Libero J Bartolotti, Arthur R Frampton, Andrea J Bourdelais, Sridhar Varadarajan
DNA-alkylating drugs continue to remain an important weapon in the arsenal against cancers. However, they typically suffer from several shortcomings because of the indiscriminate DNA damage that they cause and their inability to specifically target cancer cells. We have developed a strategy for overcoming the deficiencies in current DNA-alkylating chemotherapy drugs by designing a site-specific DNA-methylating agent that can target cancer cells because of its selective uptake via glucose transporters, which are overexpressed in most cancers...
January 3, 2017: Biochemistry
https://www.readbyqxmd.com/read/27984051/brain-endothelial-dysfunction-following-pyrithiamine-induced-thiamine-deficiency-in-the-rat
#10
Sumit Sarkar, Serguei Liachenko, Merle G Paule, John Bowyer, Joseph P Hanig
Prolonged vitamin B1 (thiamine) deficiency can lead to neurological disorders such as Wernicke's encephalopathy and Wernicke-Korsakoff Syndrome (WKS) in humans. These thiamine deficiency disorders have been attributed to vascular leakage, blood-brain barrier breakdown and neuronal loss in the diencephalon and brain stem. However, endothelial dysfunction following thiamine deficiency and its relationship to the phenomenon of neurodegeneration has not been clearly elucidated. The present study sought to begin to address this issue by evaluating vascular morphology and integrity in a pyrithiamine (PT)-induced rat model of thiamine deficiency...
October 28, 2016: Neurotoxicology
https://www.readbyqxmd.com/read/27975114/the-ketogenic-diet-a-practical-guide-for-pediatricians
#11
Aimee F Luat, Leigh Coyle, Deepak Kamat
The ketogenic diet is an effective treatment for drug-resistant epilepsies in children. In addition, it is the first-line treatment for some metabolic disorders, such as glucose transporter 1 deficiency syndrome. This article discusses the proposed mechanisms of a ketogenic diet's antiseizure action, its clinical indications, and its contraindications. The steps involved in ketogenic diet initiation, monitoring, and management of its side effects are also discussed. This review provides general pediatricians with the necessary skills to provide comprehensive care of children using the ketogenic diet and counsel their families and caregivers...
December 1, 2016: Pediatric Annals
https://www.readbyqxmd.com/read/27956522/genetic-characterization-of-the-galactitol-utilization-pathway-of-salmonella-enterica-serovar-typhimurium
#12
Nicoletta Nolle, Angela Felsl, Ralf Heermann, Thilo M Fuchs
: Galactitol degradation by salmonellae remains underinvestigated, although this metabolic capability contributes to growth in animals (1). The genes responsible for this metabolic capability are part of a 9.6-kb gene cluster that spans from gatY to gatR (STM3253 to STM3262) and encodes a phosphotransferase system, four enzymes, and a transporter of the major facilitator superfamily. Genome comparison revealed the presence of this genetic determinant in nearly all Salmonella strains. The generation time of Salmonella enterica serovar Typhimurium (S Typhimurium) strain ST4/74 was higher in minimal medium with galactitol than with glucose...
December 12, 2016: Journal of Bacteriology
https://www.readbyqxmd.com/read/27955868/engineered-kluyveromyces-marxianus-for-pyruvate-production-at-elevated-temperature-with-simultaneous-consumption-of-xylose-and-glucose
#13
Biao Zhang, Yelin Zhu, Jia Zhang, Dongmei Wang, Lianhong Sun, Jiong Hong
Xylose and glucose from lignocellulose are sustainable sources for production of pyruvate, which is the starting material for the synthesis of many drugs and agrochemicals. In this study, the pyruvate decarboxylase gene (KmPDC1) and glycerol-3-phosphate dehydrogenase gene (KmGPD1) of Kluyveromyces marxianus YZJ051 were disrupted to prevent ethanol and glycerol accumulation. The deficient growth of PDC disruption was rescued by overexpressing mutant KmMTH1-ΔT. Then pentose phosphate pathway and xylitol dehydrogenase SsXYL2-ARS genes were overexpressed to obtain strain YZB053 which produced pyruvate with xylose other than glucose...
January 2017: Bioresource Technology
https://www.readbyqxmd.com/read/27929465/using-multi-fluorinated-bile-acids-and-in-vivo-magnetic-resonance-imaging-to-measure-bile-acid-transport
#14
Jessica Felton, Kunrong Cheng, Anan Said, Aaron C Shang, Su Xu, Diana Vivian, Melissa Metry, James E Polli, Jean-Pierre Raufman
Along with their traditional role as detergents that facilitate fat absorption, emerging literature indicates that bile acids are potent signaling molecules that affect multiple organs; they modulate gut motility and hormone production, and alter vascular tone, glucose metabolism, lipid metabolism, and energy utilization. Changes in fecal bile acids may alter the gut microbiome and promote colon pathology including cholerrheic diarrhea and colon cancer. Key regulators of fecal bile acid composition are the small intestinal Apical Sodium-dependent Bile Acid Transporter (ASBT) and fibroblast growth factor-19 (FGF19)...
November 27, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27927575/novel-mutation-in-a-patient-with-late-onset-glut1-deficiency-syndrome
#15
Sandra Juozapaite, Ruta Praninskiene, Birute Burnyte, Laima Ambrozaityte, Birute Skerliene
Glucose transporter 1 deficiency syndrome (GLUT1-DS) is an inborn error of metabolism caused by impaired glucose transport through blood brain barrier due to mutation in SLC2A1 gene, encoding transporter protein. Clinical spectrum includes various signs and symptoms, ranging from severe epileptic encephalopathy to movement disorders. The diagnosis of GLUT1-DS requires hypoglycorrhachia in the presence of normoglycaemia with a reduced cerebrospinal fluid (CSF):plasma glucose ratio. The absence of pathogenic mutation in SLC2A1 gene does not exclude the diagnosis...
December 5, 2016: Brain & Development
https://www.readbyqxmd.com/read/27921254/the-impact-of-vitamin-d-supplementation-on-neurodegeneration-tnf-%C3%AE-concentration-in-hypothalamus-and-csf-to-plasma-ratio-of-insulin-in-high-fat-diet-induced-obese-rats
#16
Ghazaleh Nameni, Ghazaleh Hajiluian, Parviz Shahabi, Mahdieh Abbasalizad Farhangi, Mehran Mesgari-Abbasi, Mohammad-Reza Hemmati, Seyed Mahdi Vatandoust
There is growing evidence that obesity can lead to neurodegeneration induced by pro-inflammatory cytokines such as tumor necrosis factor (TNF-α). Moreover, obesity is associated with reduced transport of insulin through the blood-brain barrier (BBB). Insulin deficiency in the brain especially in the hypothalamus region has neurodegenerative and obesity-promoting effects. Because of the anti-inflammatory and neuroprotective effects of vitamin D, in the current experimental study, we aimed to investigate the effects of vitamin D supplementation on neurodegeneration, TNF-α concentration in the hypothalamus, and cerebrospinal fluid (CSF) to serum ratio of insulin in high-fat-diet-induced obese rats...
December 6, 2016: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/27894955/blocking-preferential-glucose-uptake-sensitizes-liver-tumor-initiating-cells-to-glucose-restriction-and-sorafenib-treatment
#17
Hui-Lu Zhang, Ming-Da Wang, Xu Zhou, Chen-Jie Qin, Gong-Bo Fu, Liang Tang, Han Wu, Shuai Huang, Ling-Hao Zhao, Min Zeng, Jiao Liu, Dan Cao, Lin-Na Guo, Hong-Yang Wang, He-Xin Yan, Jie Liu
Cancer cells display altered metabolic phenotypes characterized by a high level of glycolysis, even under normoxic conditions. Because of a high rate of glycolytic flux and inadequate vascularization, tumor cells often suffer from nutrient deficiency and require metabolic adaptations to address such stresses. Although tumor-initiating cells (T-ICs) have been identified in various malignancies, the cells' metabolic phenotypes remain elusive. In this study, we observed that liver T-ICs preferentially survived under restricted glucose treatment...
November 26, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27864142/glycogen-storage-disease-type-ib-neutrophils-exhibit-impaired-cell-adhesion-and-migration
#18
Goo-Young Kim, Young Mok Lee, Joon Hyun Kwon, Hyun Sik Jun, Janice Chou
Glycogen storage disease type Ib (GSD-Ib), characterized by impaired glucose homeostasis, neutropenia, and neutrophil dysfunction, is an inherited autosomal recessive disorder caused by a deficiency in the glucose-6-phosphate transporter (G6PT). Neutrophils play an essential role in the defense against invading pathogens. The recruitment of neutrophils towards the inflammation sites in response to inflammatory stimuli is a tightly regulated process involving rolling, adhesion, and transmigration. In this study, we investigated the role of G6PT in neutrophil adhesion and migration using in vivo and in vitro models...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27856334/quantitative-metabolic-flux-analysis-reveals-an-unconventional-pathway-of-fatty-acid-synthesis-in-cancer-cells-deficient-for-the-mitochondrial-citrate-transport-protein
#19
Lei Jiang, Adam Boufersaoui, Chendong Yang, Bookyung Ko, Dinesh Rakheja, Gerardo Guevara, Zeping Hu, Ralph J DeBerardinis
The mitochondrial citrate transport protein (CTP), encoded by SLC25A1, accommodates bidirectional trafficking of citrate between the mitochondria and cytosol, supporting lipid biosynthesis and redox homeostasis. Genetic CTP deficiency causes a fatal neurodevelopmental syndrome associated with the accumulation of L- and D-2-hydroxyglutaric acid, and elevated CTP expression is associated with poor prognosis in several types of cancer, emphasizing the importance of this transporter in multiple human pathologies...
November 14, 2016: Metabolic Engineering
https://www.readbyqxmd.com/read/27814392/gender-specific-mechanisms-underlying-the-amelioration-of-high-fat-diet-induced-glucose-intolerance-in-b-cell-activating-factor-deficient-mice
#20
Bobae Kim, Chang-Kee Hyun
It has recently been found that B cell activating factor (BAFF) plays an important role in the regulation of energy homeostasis. We also have previously reported that BAFF deficiency reverses high-fat (HF) diet-induced glucose intolerance by potentiating adipose tissue function. In the present study, we found that BAFF deficient (BAFF-/-) mice exhibit gender-specific differences in protection against diet-induced glucose intolerance, and aimed to characterize the gender-dependent molecular alterations in energy metabolism...
2016: PloS One
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