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https://www.readbyqxmd.com/read/28542610/gpr40-partial-agonist-mk-2305-lower-fasting-glucose-in-the-goto-kakizaki-rat-via-suppression-of-endogenous-glucose-production
#1
Corin Miller, Michele J Pachanski, Melissa E Kirkland, Daniel T Kosinski, Joel Mane, Michelle Bunzel, Jin Cao, Sarah Souza, Brande Thomas-Fowlkes, Jerry Di Salvo, Adam B Weinglass, Xiaoyan Li, Robert W Myers, Kevin Knagge, Paul E Carrington, William K Hagmann, Maria E Trujillo
GPR40 (FFA1) is a fatty acid receptor whose activation results in potent glucose lowering and insulinotropic effects in vivo. Several reports illustrate that GPR40 agonists exert glucose lowering in diabetic humans. To assess the mechanisms by which GPR40 partial agonists improve glucose homeostasis, we evaluated the effects of MK-2305, a potent and selective partial GPR40 agonist, in diabetic Goto Kakizaki rats. MK-2305 decreased fasting glucose after acute and chronic treatment. MK-2305-mediated changes in glucose were coupled with increases in plasma insulin during hyperglycemia and glucose challenges but not during fasting, when glucose was normalized...
2017: PloS One
https://www.readbyqxmd.com/read/28542447/exploratory-plasma-proteomic-analysis-in-a-randomized-crossover-trial-of-aspirin-among-healthy-men-and-women
#2
Xiaoliang Wang, Ali Shojaie, Yuzheng Zhang, David Shelley, Paul D Lampe, Lisa Levy, Ulrike Peters, John D Potter, Emily White, Johanna W Lampe
Long-term use of aspirin is associated with lower risk of colorectal cancer and other cancers; however, the mechanism of chemopreventive effect of aspirin is not fully understood. Animal studies suggest that COX-2, NFκB signaling and Wnt/β-catenin pathways may play a role, but no clinical trials have systematically evaluated the biological response to aspirin in healthy humans. Using a high-density antibody array, we assessed the difference in plasma protein levels after 60 days of regular dose aspirin (325 mg/day) compared to placebo in a randomized double-blinded crossover trial of 44 healthy non-smoking men and women, aged 21-45 years...
2017: PloS One
https://www.readbyqxmd.com/read/28542252/metabolic-flux-analysis-of-heterotrophic-growth-in-chlamydomonas-reinhardtii
#3
Nanette R Boyle, Neelanjan Sengupta, John A Morgan
Despite the wealth of knowledge available for C. reinhardtii, the central metabolic fluxes of growth on acetate have not yet been determined. In this study, 13C-metabolic flux analysis (13C-MFA) was used to determine and quantify the metabolic pathways of primary metabolism in C. reinhardtii cells grown under heterotrophic conditions with acetate as the sole carbon source. Isotopic labeling patterns of compartment specific biomass derived metabolites were used to calculate the fluxes. It was found that acetate is ligated with coenzyme A in the three subcellular compartments (cytosol, mitochondria and plastid) included in the model...
2017: PloS One
https://www.readbyqxmd.com/read/28537741/an-optimized-extraction-method-to-remove-humic-acids-interferences-from-soil-samples-prior-to-microbial-proteome-measurements
#4
Chen Qian, Robert L Hettich
The microbial composition and their activities in soil environments play a critical role in organic matter transformation and nutrient cycling. Liquid chromatography coupled to high performance mass spectrometry provides a powerful approach to characterize soil microbiomes; however, the limited microbial biomass and the presence of abundant interferences in soil samples present major challenges to proteome extraction and subsequent MS measurement. To this end, we have designed an experimental method to improve microbial proteome measurement by removing the soil-borne humic substances co-extraction from soils...
May 24, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28535757/intracellular-product-recycling-in-high-succinic-acid-producing-yeast-at-low-ph
#5
S Aljoscha Wahl, Cristina Bernal Martinez, Zheng Zhao, Walter M van Gulik, Mickel L A Jansen
BACKGROUND: The metabolic engineering of Saccharomyces cerevisiae for the production of succinic acid has progressed dramatically, and a series of high-producing hosts are available. At low cultivation pH and high titers, the product transport can become bidirectional, i.e. the acid is reentering the cell and is again exported or even catabolized. Here, a quantitative approach for the identification of product recycling fluxes is developed. RESULTS: The metabolic flux distributions at two time-points of the fermentation process were analyzed...
May 23, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28535465/altered-glycometabolism-in-zebrafish-exposed-to-thifluzamide
#6
Yang Yang, Wenxian Liu, Dongzhi Li, Le Qian, Bin Fu, Chengju Wang
Thifluzamide exerts toxic effects to zebrafish and causes liver mitochondrial damage. To better understand the further mechanism, adult zebrafish were exposed to a range of thifluzamide concentrations (0, 0.019, 0.19, and 1.90 mg/L) for 28 days. In response to 1.90 mg/L exposure, liver glycogen significantly increased and blood glucose decreased. The expression of genes related to glycometabolism showed corresponding changes. Genes related to mtDNA replication and transcription and genes participating in mitochondrial complexes showed altered expression, which might lead to the inhibition of the tricarboxylic acid cycle (TCA)...
May 10, 2017: Chemosphere
https://www.readbyqxmd.com/read/28520899/increased-urinary-trimethylamine-n-oxide-tmao-following-cryptosporidium-infection-and-protein-malnutrition-independent-of-microbiome-effects
#7
D T Bolick, J Mayneris-Perxachs, G L Medlock, G L Kolling, J Papin, J R Swann, R L Guerrant
Cryptosporidium infections have been associated with growth stunting even in the absence of diarrhea. Having previously detailed the effects of protein deficiency on both microbiome and metabolome in this model, we now describe the specific gut microbial and biochemical effects of Cryptosporidium infection. Protein deficient mice were infected with Cryptosporidium parvum oocysts for 6-13 days and compared to uninfected controls. Following infection there was an increase in the urinary excretion of choline- and amino acid-derived metabolites...
May 17, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28520815/metabolic-profiling-by-gas-chromatography-mass-spectrometry-of-energy-metabolism-in-high-fat-diet-fed-obese-mice
#8
Daxesh P Patel, Kristopher W Krausz, Cen Xie, Diren Beyoğlu, Frank J Gonzalez, Jeffrey R Idle
A novel, selective and sensitive single-ion monitoring (SIM) gas chromatography-mass spectrometry (GCMS) method was developed and validated for the determination of energy metabolites related to glycolysis, the tricarboxylic acid (TCA) cycle, glutaminolysis, and fatty acid β-oxidation. This assay used N-tert-butyldimethylsilyl-N-methyltrifluoroacetamide (MTBSTFA) containing 1% tert-butyldimethylchlorosilane (TBDMCS) as derivatizing reagent and was highly reproducible, sensitive, specific and robust. The assay was used to analyze liver tissue and serum from C57BL/6N obese mice fed a high-fat diet (HFD) and C57BL/6N mice fed normal chow for 8 weeks...
2017: PloS One
https://www.readbyqxmd.com/read/28512469/metabolic-perturbation-and-potential-markers-in-patients-with-esophageal-cancer
#9
Xianlan Zhu, Kun Wang, Gaoshuang Liu, Yuqing Wang, Jin Xu, Linsheng Liu, Mengjie Li, Jian Shi, Jiye Aa, Lianzhen Yu
Clinical diagnosis of esophageal cancer (EC) at early stage is rather difficult. This study aimed to profile the molecules in serum and tissue and identify potential biomarkers in patients with EC. A total of 64 volunteers were recruited, and 83 samples (24 EC serum samples, 21 serum controls, 19 paired EC tissues, and corresponding tumor-adjacent tissues) were analyzed. The gas chromatography time-of-flight mass spectrometry (GC/TOF-MS) was employed, and principal component analysis was used to reveal the discriminatory metabolites and identify the candidate markers of EC...
2017: Gastroenterology Research and Practice
https://www.readbyqxmd.com/read/28508886/protein-protein-interactions-and-metabolite-channelling-in-the-plant-tricarboxylic-acid-cycle
#10
Youjun Zhang, Katherine F M Beard, Corné Swart, Susan Bergmann, Ina Krahnert, Zoran Nikoloski, Alexander Graf, R George Ratcliffe, Lee J Sweetlove, Alisdair R Fernie, Toshihiro Obata
Protein complexes of sequential metabolic enzymes, often termed metabolons, may permit direct channelling of metabolites between the enzymes, providing increased control over metabolic pathway fluxes. Experimental evidence supporting their existence in vivo remains fragmentary. In the present study, we test binary interactions of the proteins constituting the plant tricarboxylic acid (TCA) cycle. We integrate (semi-)quantitative results from affinity purification-mass spectrometry, split-luciferase and yeast-two-hybrid assays to generate a single reliability score for assessing protein-protein interactions...
May 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28501380/crispri-mediated-phosphoenolpyruvate-carboxylase-regulation-to-enhance-the-production-of-lipid-in-chlamydomonas-reinhardtii
#11
Pei-Hsun Kao, I-Son Ng
In this study, CRISPRi (clustered regularly interspaced short palindromic repeats interference) was used for the first time to regulate expression of exogenously supplied rfp gene as a proof-of-concept, and endogenous PEPC1 gene as a proof-of-function in Chlamydomonas reinhardtii. The efficiency of 94% and stability of 7 generations via CRISPRi mediated gene regulation in C. reinhardtii have been demonstrated by RFP. Gene PEPC1 encoding proteins are essential for controlling the carbon flux that enters the TCA cycle and plays a crucial role in carbon partitioning of substrates in competition with lipid synthesis...
May 4, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28501379/metabolic-impact-of-nutrient-starvation-in-mevalonate-producing-escherichia-coli
#12
Ami Masuda, Yoshihiro Toya, Hiroshi Shimizu
The aim of this work was to enhance mevalonate yield from glucose in Escherichia coli by essential nutrient starvations and to reveal these effects on the central carbon metabolism. Stationary phase culture without essential nutrients such as nitrogen, sulfur, and magnesium was evaluated using an engineered E. coli introducing mvaE and mvaS genes from Enterococcus faecalis. Sulfur starvation resulted in the highest mevalonate yield of 0.61C-molC-mol(-1) from glucose. The metabolic impacts of nutrient starvation were investigated by (13)C-metabolic flux analysis...
May 4, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28497127/evidence-of-glycolysis-up-regulation-and-pyruvate-mitochondrial-oxidation-mismatch-during-mechanical-unloading-of-the-failing-human-heart-implications-for-cardiac-reloading-and-conditioning
#13
Nikolaos A Diakos, Sutip Navankasattusas, E Dale Abel, Jared Rutter, Lauren McCreath, Peter Ferrin, Stephen H McKellar, Dylan V Miller, Song Y Park, Russell S Richardson, Ralph Deberardinis, James E Cox, Abdallah G Kfoury, Craig H Selzman, Josef Stehlik, James C Fang, Dean Y Li, Stavros G Drakos
This study sought to investigate the effects of mechanical unloading on myocardial energetics and the metabolic perturbation of heart failure (HF) in an effort to identify potential new therapeutic targets that could enhance the unloading-induced cardiac recovery. The authors prospectively examined paired human myocardial tissue procured from 31 advanced HF patients at left ventricular assist device (LVAD) implant and at heart transplant plus tissue from 11 normal donors. They identified increased post-LVAD glycolytic metabolites without a coordinate increase in early, tricarboxylic acid (TCA) cycle intermediates...
October 2016: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/28493687/comparative-metabolic-response-between-cucumber-cucumis-sativus-and-corn-zea-mays-to-a-cu-oh-2-nanopesticide
#14
Lijuan Zhao, Yuxiong Huang, Arturo A Keller
Due to their unique properties, copper-based nanopesticides are emerging in the market. Thus, understanding their effect on crop plants is very important. Metabolomics can capture a snapshot of cellular metabolic responses to a stressor. We selected maize and cucumber as model plants for exposure to different doses of Cu(OH)2 nanopesticide. GC-TOF-MS-based metabolomics was employed to determine the metabolic responses of these two species. Results revealed significant differences in metabolite profile changes between maize and cucumber...
May 17, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28488414/a-proteomic-based-investigation-of-potential-copper-responsive-biomarkers-proteins-conceptual-networks-and-metabolic-pathways-featuring-penicillium-janthinellum-from-a%C3%A2-heavy-metal-polluted-ecological-niche
#15
Xin Feng, Jian Xu, Yu Liang, Guo-Li Chen, Xian-Wei Fan, You-Zhi Li
Filamentous fungi-copper (Cu) interactions are very important in the formation of natural ecosystems and the bioremediation of heavy metal pollution. However, important issues at the proteome level remain unclear. We compared six proteomes from Cu-resistant wild-type (WT) Penicillium janthinellum strain GXCR and a Cu-sensitive mutant (EC-6) under 0, 0.5, and 3 mmol/L Cu treatments using iTRAQ. A total of 495 known proteins were identified, and the following conclusions were drawn from the results: Cu tolerance depends on ATP generation and supply, which is relevant to glycolysis pathway activity; oxidative phosphorylation, the TCA cycle, gluconeogenesis, fatty acid synthesis, and metabolism are also affected by Cu; high Cu sensitivity is primarily due to an ATP energy deficit; among ATP generation pathways, Cu-sensitive and Cu-insensitive metabolic steps exist; gluconeogenesis pathway is crucial to the survival of fungi in Cu-containing and sugar-scarce environments; fungi change their proteomes via two routes (from ATP, ATP-dependent RNA helicases (ADRHs), and ribosome biogenesis to proteasomes and from ATP, ADRHs to spliceosomes and/or stress-adapted RNA degradosomes) to cope with changes in Cu concentrations; and unique routes exist through which fungi respond to high environmental Cu...
May 9, 2017: MicrobiologyOpen
https://www.readbyqxmd.com/read/28481733/tissue-proteome-analysis-of-different-grades-of-human-gliomas-provides-major-cues-for-glioma-pathogenesis
#16
Kishore Gollapalli, Saicharan Ghantasala, Apurva Atak, Srikanth Rapole, Aliasgar Moiyadi, Sridhar Epari, Sanjeeva Srivastava
Gliomas are heterogeneous and most commonly occurring brain tumors. Blood-brain barrier restricts the entry of brain tumor proteins into blood stream thus limiting the usage of serum or plasma for proteomic analysis. Our study aimed at understanding the molecular basis of aggressiveness of various grades of brain tumors using isobaric tagging for relative and absolute quantification (iTRAQ) based mass spectrometry. Tissue proteomic analysis of various grades of gliomas was performed using four-plex iTRAQ. We labeled five sets (each set consists of control, grade-II, III, and IV tumor samples) of individual glioma patients using iTRAQ reagents...
May 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28475111/riboflavin-responsive-mitochondrial-dysfunction-in-neurodegenerative-diseases
#17
REVIEW
Tamilarasan Udhayabanu, Andreea Manole, Mohan Rajeshwari, Perumal Varalakshmi, Henry Houlden, Balasubramaniem Ashokkumar
Mitochondria are the repository for various metabolites involved in diverse energy-generating processes, like the TCA cycle, oxidative phosphorylation, and metabolism of amino acids, fatty acids, and nucleotides, which rely significantly on flavoenzymes, such as oxidases, reductases, and dehydrogenases. Flavoenzymes are functionally dependent on biologically active flavin adenine dinucleotide (FAD) or flavin mononucleotide (FMN), which are derived from the dietary component riboflavin, a water soluble vitamin...
May 5, 2017: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/28472361/energy-metabolism-of-the-osteoblast-implications-for-osteoporosis
#18
Wen-Chih Lee, Anyonya R Guntur, Fanxin Long, Clifford J Rosen
Osteoblasts, the bone forming cells of the remodeling unit, are essential for growth and maintenance of the skeleton. Clinical disorders of substrate availability (e.g. diabetes mellitus, anorexia nervosa and aging) cause osteoblast dysfunction ultimately leading to skeletal fragility and osteoporotic fractures. Conversely, anabolic treatments for osteoporosis enhance the work of the osteoblast by altering osteoblast metabolism. Emerging evidence supports glycolysis as the major metabolic pathway to meet ATP demand during osteoblast differentiation...
May 1, 2017: Endocrine Reviews
https://www.readbyqxmd.com/read/28467784/in-silico-gene-expression-analysis-reveals-glycolysis-and-acetate-anaplerosis-in-idh1-wild-type-glioma-and-lactate-and-glutamate-anaplerosis-in-idh1-mutated-glioma
#19
Mohammed Khurshed, Remco J Molenaar, Krissie Lenting, William P Leenders, Cornelis J F van Noorden
Hotspot mutations in isocitrate dehydrogenase 1 (IDH1) initiate low-grade glioma and secondary glioblastoma and induce a neomorphic activity that converts α-ketoglutarate (α-KG) to the oncometabolite D-2-hydroxyglutarate (D-2-HG). It causes metabolic rewiring that is not fully understood. We investigated the effects of IDH1 mutations (IDH1MUT) on expression of genes that encode for metabolic enzymes by data mining The Cancer Genome Atlas. We analyzed 112 IDH1 wild-type (IDH1WT) versus 399 IDH1MUT low-grade glioma and 157 IDH1WT versus 9 IDH1MUT glioblastoma samples...
April 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28467421/a-fungal-transcription-factor-essential-for-starch-degradation-affects-integration-of-carbon-and-nitrogen-metabolism
#20
Yi Xiong, Vincent W Wu, Andrea Lubbe, Lina Qin, Siwen Deng, Megan Kennedy, Diane Bauer, Vasanth R Singan, Kerrie Barry, Trent R Northen, Igor V Grigoriev, N Louise Glass
In Neurospora crassa, the transcription factor COL-26 functions as a regulator of glucose signaling and metabolism. Its loss leads to resistance to carbon catabolite repression. Here, we report that COL-26 is necessary for the expression of amylolytic genes in N. crassa and is required for the utilization of maltose and starch. Additionally, the Δcol-26 mutant shows growth defects on preferred carbon sources, such as glucose, an effect that was alleviated if glutamine replaced ammonium as the primary nitrogen source...
May 3, 2017: PLoS Genetics
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