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Glucokinase

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https://www.readbyqxmd.com/read/28810182/selenium-increases-hepatic-dna-methylation-and-modulates-one-carbon-metabolism-in-the-liver-of-mice
#1
Bodo Speckmann, Sarah Schulz, Franziska Hiller, Deike Hesse, Fabian Schumacher, Burkhard Kleuser, Jürgen Geisel, Rima Obeid, Tilman Grune, Anna P Kipp
The average intake of the essential trace element selenium (Se) is below the recommendation in most European countries, possibly causing sub-optimal expression of selenoproteins. It is still unclear how a suboptimal Se status may affect health. To mimic this situation, mice were fed one of three physiologically relevant amounts of Se. We focused on the liver, the organ most sensitive to changes in the Se supply indicated by hepatic glutathione peroxidase activity. In addition, liver is the main organ for synthesis of methyl groups and glutathione via one-carbon metabolism...
July 9, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28800453/discovery-of-cycloalkyl-fused-n-thiazol-2-yl-benzamides-as-tissue-non-specific-glucokinase-activators-design-synthesis-and-biological-evaluation
#2
Zhengyu Wang, Xiaofan Shi, Huan Zhang, Liang Yu, Yanhua Cheng, Hefeng Zhang, Huibin Zhang, Jinpei Zhou, Jing Chen, Xu Shen, Wenhu Duan
Glucokinase (GK) activators are being developed for the treatment of type 2 diabetes mellitus (T2DM). However, existing GK activators have risks of hypoglycemia caused by over-activation of GK in islet cells and dyslipidemia caused by over-activation of intrahepatic GK. In the effort to mitigate risks of hypoglycemia and dyslipidemia while maintaining the promising efficacy of GK activator, we investigated a series of cycloalkyl-fused N-thiazol-2-yl-benzamides as tissue non-specific partial GK activators, which led to the identification of compound 72 that showed a good balance between in vitro potency and enzyme kinetic parameters, and protected β-cells from streptozotocin-induced apoptosis...
July 25, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28765812/role-of-ampd2-in-impaired-glucose-tolerance-induced-by-high-fructose-diet
#3
Athanasius Wrin Hudoyo, Tetsuaki Hirase, Andreas Tandelillin, Masahiko Honda, Manabu Shirai, Jidong Cheng, Hiroko Morisaki, Takayuki Morisaki
A high intake of products containing fructose is known to mediate insulin resistance. In the liver, AMPD2, an isoform of AMPD, has important glucose metabolic homeostasis functions including maintenance of AMP-activated protein kinase (AMPK). We speculated that AMPD2 induces impaired glucose tolerance in individuals who consume a high-fructose diet. We gave either a normal-chow (NCD) or high-fructose (HFrD) diet for 40 days to 8-week-old male wild-type (WT) and Ampd2 -/- homozygote (A2 -/-) C57BL/6 mice...
December 2017: Molecular Genetics and Metabolism Reports
https://www.readbyqxmd.com/read/28762642/genomic-transcriptional-and-phenotypic-analysis-of-the-glucose-derepressed-clostridium-beijerinckii-mutant-exhibiting-acid-crash-phenotype
#4
Seung-Oh Seo, Holger Janssen, Andrew Magis, Yi Wang, Ting Lu, Nathan D Price, Yong-Su Jin, Hans P Blaschek
Clostridium beijerinckii is a predominant solventogenic bacterium that has been used for the ABE fermentation. Various C. beijerinckii mutants have been constructed for desirable phenotypes. The C. beijerinckii mutant BA105 harboring a glucose derepression phenotype was previously isolated and demonstrated the enhanced amylolytic activity in the presence of glucose. Despite its potential use, BA105 has not been further characterized and utilized. Therefore, we investigated fermentation phenotypes of BA105 in this study...
August 1, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/28754456/hdl-cholesterol-ldl-cholesterol-and-triglycerides-as-risk-factors-for-ckd-a-mendelian-randomization-study
#5
Matthew B Lanktree, Sébastien Thériault, Michael Walsh, Guillaume Paré
BACKGROUND: High-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride concentrations are heritable risk factors for vascular disease, but their role in the progression of chronic kidney disease (CKD) is unclear. STUDY DESIGN: 2-sample Mendelian randomization analysis of data derived from the largest published lipid and CKD studies. SETTING & PARTICIPANTS: Effect of independent genetic variants significantly associated with lipid concentrations was obtained from the Global Lipids Genetics Consortium (n=188,577), and the effect of these same variants on estimated glomerular filtration rate (eGFR), CKD (defined as eGFR<60mL/min/1...
July 26, 2017: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/28727166/hepatocytes-contribute-to-residual-glucose-production-in-a-mouse-model-for-glycogen-storage-disease-type-ia
#6
Brenda S Hijmans, Andreas Boss, Theo H van Dijk, Maud Soty, Henk Wolters, Elodie Mutel, Albert K Groen, Terry G J Derks, Gilles Mithieux, Arend Heerschap, Dirk-Jan Reijngoud, Fabienne Rajas, Maaike H Oosterveer
It is a longstanding enigma how glycogen storage disease (GSD) type I patients retain a limited capacity for endogenous glucose production (EGP) despite the loss of glucose-6-phosphatase (G6Pase) activity. Insight into the source of residual EGP is of clinical importance given the risk of sudden death in these patients, but so far contradictory mechanisms have been proposed. We investigated G6Pase-independent EGP in hepatocytes isolated from a liver-specific GSD Ia mouse model (L-G6pc(-/-) mice), and performed real-time analysis of hepatic glucose fluxes and glycogen metabolism in L-G6pc(-/-) mice using state-of-the-art stable isotope methodologies...
July 20, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28726111/glucokinase-mutations-in-pediatric-patients-with-impaired-fasting-glucose
#7
C Aloi, A Salina, N Minuto, R Tallone, F Lugani, A Mascagni, O Mazza, M Cassanello, M Maghnie, G d'Annunzio
AIMS: Our aim was to detect the frequency of glucokinase (GCK) gene mutations in a cohort of patients with impaired fasting glucose and to describe the clinical manifestations of identified variants. We also aimed at predicting the effect of the novel missense mutations by computational approach. METHODS: Overall 100 unrelated Italian families with impaired fasting glucose were enrolled and subdivided into two cohorts according to strict and to mild criteria for diagnosis of maturity-onset diabetes of the young (MODY)...
July 19, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28701865/processed-panax-ginseng-sun-ginseng-inhibits-the-differentiation-and-proliferation-of-3t3-l1-preadipocytes-and-fat-accumulation-in-caenorhabditis-elegans
#8
Hyejin Lee, Jinhee Kim, Jun Yeon Park, Ki Sung Kang, Joeng Hill Park, Gwi Seo Hwang
BACKGROUND: Heat-processed ginseng, sun ginseng (SG), has been reported to have improved therapeutic properties compared with raw forms, such as increased antidiabetic, anti-inflammatory, and antihyperglycemic effects. The aim of this study was to investigate the antiobesity effects of SG through the suppression of cell differentiation and proliferation of mouse 3T3-L1 preadipocyte cells and the lipid accumulation in Caenorhabditis elegans. METHODS: To investigate the effect of SG on adipocyte differentiation, levels of stained intracellular lipid droplets were quantified by measuring the oil red O signal in the lipid extracts of cells on differentiation Day 7...
July 2017: Journal of Ginseng Research
https://www.readbyqxmd.com/read/28683826/identification-and-characterization-of-a-foxa2-regulated-transcriptional-enhancer-at-a-type-2-diabetes-intronic-locus-that-controls-gckr-expression-in-liver-cells
#9
Maykel López Rodríguez, Dorota Kaminska, Kati Lappalainen, Jussi Pihlajamäki, Minna U Kaikkonen, Markku Laakso
BACKGROUND: Genome-wide association studies (GWAS) have identified more than 100 genetic loci associated with type 2 diabetes (T2D). However, the underlying biological mechanisms for many of these associations remain unknown. GWAS signals close to the glucokinase regulatory protein gene (GCKR) have been reported for lipid and glucose metabolism traits and the risk of T2D. We investigated the regulatory function of an intronic locus at GCKR represented by the lead single nucleotide polymorphism (SNP) rs780094...
July 6, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28678435/molecular-mechanisms-of-action-of-styrene-toxicity-in-blood-plasma-and-liver
#10
Kamal Niaz, Faheem Mabqool, Fazlullah Khan, Fatima Ismail Hassan, Maryam Baeeri, Mona Navaei-Nigjeh, Shokoufeh Hassani, Mahdi Gholami, Mohammad Abdollahi
Styrene is an aromatic colorless hydrocarbon available in liquid form and highly volatile. In its pure form, it gives a sweet smell. The primary source of exposure in the environment is from plastic materials, rubber industries, packaging materials, insulations, and fiber glass and carpet industry. Natural sources of styrene include: few metabolites in plants which are transferred through food chain. The current study was designed to evaluate styrene toxicity, including: superoxide dismutase (SOD) and protein carbonyl, oxidative stress, glucose-6-phosphatase (G6Pase), glycogen phosphorylase (GP), and phosphoenolpyruvate carboxykinase (PEPCK) activities, adenosine triphosphate (ATP) to adenosine diphosphate (ADP) ratio, and changes in gene expressions such as glutamate dehydrogenase 1 (GLUD1), glucose transporter 2 (GLUT2), and glucokinase (GCK) in the rat liver tissue...
July 5, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28663157/phenotype-heterogeneity-in-glucokinase-maturity-onset-diabetes-of-the-young-gck-mody-patients-single-pediatric-centre-observation
#11
Anna Wedrychyowicz, Ewa Tobor, Magdalena Wilk, Ewa Ziolkowska-Ledwith, Anna Rams, Katarzyna Wzorek, Barbara Sabal, Małgorzata Stelmach, Jerzy B Starzyk
OBJECTIVE: The aim of the study was to evaluate the clinical phenotypes of Glucokinase - Maturity Onset Diabetes of the Young (GCK-MODY) pediatric patients from South-West Poland and to search for phenotype-genotype correlations. METHODS: We performed retrospective analysis of data of all 37 CGK-MODY patients, 21 girls, age 1.9-20.1, mean 12.5±5.2 years, treated in our centre. A retrospective analysis of clinical data from years 2002-2013 was performed. RESULTS: GCK-MODY carriers were found among 1043 diabetes mellitus (DM) patients (3%), they were second the most numerous groups of DM patients, following type 1 DM, in our centre...
June 30, 2017: Journal of Clinical Research in Pediatric Endocrinology
https://www.readbyqxmd.com/read/28655753/the-thermodynamic-basis-of-glucose-stimulated-insulin-release-a-model-of-the-core-mechanism
#12
David F Wilson, Abigail T J Cember, Franz M Matschinsky
A model for glucose sensing by pancreatic β-cells is developed and compared with the available experimental data. The model brings together mathematical representations for the activities of the glucose sensor, glucokinase, and oxidative phosphorylation. Glucokinase produces glucose 6-phosphate (G-6-P) in an irreversible reaction that determines glycolytic flux. The primary products of glycolysis are NADH and pyruvate. The NADH is reoxidized and the reducing equivalents transferred to oxidative phosphorylation by the glycerol phosphate shuttle, and some of the pyruvate is oxidized by pyruvate dehydrogenase and enters the citric acid cycle...
June 2017: Physiological Reports
https://www.readbyqxmd.com/read/28648619/nuclear-import-of-glucokinase-in-pancreatic-beta-cells-is-mediated-by-a-nuclear-localization-signal-and-modulated-by-sumoylation
#13
Bente Berg Johansson, Karianne Fjeld, Marie Holm Solheim, Jun Shirakawa, Enming Zhang, Magdalena Keindl, Jiang Hu, Andreas Lindqvist, Anne Døskeland, Gunnar Mellgren, Torgeir Flatmark, Pål Rasmus Njølstad, Rohit N Kulkarni, Nils Wierup, Ingvild Aukrust, Lise Bjørkhaug
The localization of glucokinase in pancreatic beta-cell nuclei is a controversial issue. Although previous reports suggest such a localization, the mechanism for its import has so far not been identified. Using immunofluorescence, subcellular fractionation and mass spectrometry, we present evidence in support of glucokinase localization in beta-cell nuclei of human and mouse pancreatic sections, as well as in human and mouse isolated islets, and murine MIN6 cells. We have identified a conserved, seven-residue nuclear localization signal ((30)LKKVMRR(36)) in the human enzyme...
October 15, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28645481/subcellular-localization-of-glycolytic-enzymes-and-characterization-of-intermediary-metabolism-of-trypanosoma-rangeli
#14
Rocío Rondón-Mercado, Héctor Acosta, Ana J Cáceres, Wilfredo Quiñones, Juan Luis Concepción
Trypanosoma rangeli is a hemoflagellate protist that infects wild and domestic mammals as well as humans in Central and South America. Although this parasite is not pathogenic for human, it is being studied because it shares with Trypanosoma cruzi, the etiological agent of Chagas' disease, biological characteristics, geographic distribution, vectors and vertebrate hosts. Several metabolic studies have been performed with T. cruzi epimastigotes, however little is known about the metabolism of T. rangeli. In this work we present the subcellular distribution of the T...
June 20, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28640743/glucose-consumption-in-carbohydrate-mixtures-by-phosphotransferase-system-mutants-of-escherichia-coli
#15
Tian Xia, Neeraj Sriram, Sarah A Lee, Ronni Altman, Jeffrey L Urbauer, Elliot Altman, Mark A Eiteman
Escherichia coli lacking the glucose phosphotransferase system (PTS), mannose PTS and glucokinase are supposedly unable to grow on glucose as the sole carbon source (Curtis SJ, Epstein W. J Bacteriol 1975;122:1189-1199). We report that W ptsG manZ glk (ALS1406) grows slowly on glucose in media containing glucose with a second carbon source: ALS1406 metabolizes glucose after that other carbon source, including arabinose, fructose, glycerol, succinate or xylose, is exhausted. Galactose is an exception to this rule, as ALS1406 simultaneously consumes both galactose and glucose...
June 22, 2017: Microbiology
https://www.readbyqxmd.com/read/28626777/long-term-efficacy-and-safety-of-insulin-and-glucokinase-gene-therapy-for-diabetes-8-year-follow-up-in-dogs
#16
Maria Luisa Jaén, Laia Vilà, Ivet Elias, Veronica Jimenez, Jordi Rodó, Luca Maggioni, Rafael Ruiz-de Gopegui, Miguel Garcia, Sergio Muñoz, David Callejas, Eduard Ayuso, Tura Ferré, Iris Grifoll, Anna Andaluz, Jesus Ruberte, Virginia Haurigot, Fatima Bosch
Diabetes is a complex metabolic disease that exposes patients to the deleterious effects of hyperglycemia on various organs. Achievement of normoglycemia with exogenous insulin treatment requires the use of high doses of hormone, which increases the risk of life-threatening hypoglycemic episodes. We developed a gene therapy approach to control diabetic hyperglycemia based on co-expression of the insulin and glucokinase genes in skeletal muscle. Previous studies proved the feasibility of gene delivery to large diabetic animals with adeno-associated viral (AAV) vectors...
September 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28623340/adenovirus-mediated-suppression-of-hypothalamic-glucokinase-affects-feeding-behavior
#17
Romina María Uranga, Carola Millán, María José Barahona, Antonia Recabal, Magdiel Salgado, Fernando Martinez, Patricio Ordenes, Roberto Elizondo-Vega, Fernando Sepúlveda, Elena Uribe, María de Los Ángeles García-Robles
Glucokinase (GK), the hexokinase involved in glucosensing in pancreatic β-cells, is also expressed in arcuate nucleus (AN) neurons and hypothalamic tanycytes, the cells that surround the basal third ventricle (3V). Several lines of evidence suggest that tanycytes may be involved in the regulation of energy homeostasis. Tanycytes have extended cell processes that contact the feeding-regulating neurons in the AN, particularly, agouti-related protein (AgRP), neuropeptide Y (NPY), cocaine- and amphetamine-regulated transcript (CART) and proopiomelanocortin (POMC) neurons...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28615161/high-glucose-increases-action-potential-firing-of-catecholamine-neurons-in-the-nucleus-of-the-solitary-tract-by-increasing-spontaneous-glutamate-inputs
#18
Brandon L Roberts, Mingyan Zhu, Huan Zhao, Crystal Dillon, Suzanne M Appleyard
Glucose is a crucial substrate essential for cell survival and function. Changes in glucose levels impact neuronal activity and glucose deprivation increases feeding. Several brain regions have been shown to respond to glucoprivation, including the nucleus of the solitary tract (NTS) in the brainstem. The NTS is the primary site in the brain that receives visceral afferent information from the gastrointestinal tract. The catecholaminergic (CA) subpopulation within the NTS modulates many homeostatic functions including cardiovascular reflexes, respiration, food intake, arousal and stress...
June 14, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28593615/a-single-dose-of-dapagliflozin-an-sglt-2-inhibitor-induces-higher-glycosuria-in-gck-and-hnf1a-mody-than-in-type-2-diabetes-mellitus
#19
J Hohendorff, M Szopa, J Skupien, M Kapusta, B Zapala, T Platek, S Mrozinska, T Parpan, W Glodzik, A Ludwig-Galezowska, B Kiec-Wilk, T Klupa, M T Malecki
AIMS: SGLT2 inhibitors are a new class of oral hypoglycemic agents used in type 2 diabetes (T2DM). Their effectiveness in maturity onset diabetes of the young (MODY) is unknown. We aimed to assess the response to a single dose of 10 mg dapagliflozin in patients with Hepatocyte Nuclear Factor 1 Alpha (HNF1A)-MODY, Glucokinase (GCK)-MODY, and type 2 diabetes. METHODS: We examined 14 HNF1A-MODY, 19 GCK-MODY, and 12 type 2 diabetes patients. All studied individuals received a single morning dose of 10 mg of dapagliflozin added to their current therapy of diabetes...
August 2017: Endocrine
https://www.readbyqxmd.com/read/28584574/increased-glucose-metabolism-and-alpha-glucosidase-inhibition-in-cordyceps-militaris-water-extract-treated-hepg2-cells
#20
Dae Jung Kim, Yun Hwan Kang, Kyoung Kon Kim, Tae Woo Kim, Jae Bong Park, Myeon Choe
BACKGROUND/OBJECTIVES: Recent living condition improvements, changes in dietary habits, and reductions in physical activity are contributing to an increase in metabolic syndrome symptoms including diabetes and obesity. Through such societal developments, humankind is continuously exposed to metabolic diseases such as diabetes, and the number of the victims is increasing. This study investigated Cordyceps militaris water extract (CMW)-induced glucose uptake in HepG2 cells and the effect of CMW treatment on glucose metabolism...
June 2017: Nutrition Research and Practice
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