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Glucokinase

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https://www.readbyqxmd.com/read/28922469/one-pot-synthesis-of-gdp-mannose-by-a-multi-enzyme-cascade-for-enzymatic-assembly-of-lipid-linked-oligosaccharides
#1
Thomas F T Rexer, Anna Schildbach, Jan Klapproth, Angelika Schierhorn, Reza Mahour, Markus Pietzsch, Erdmann Rapp, Udo Reichl
Glycosylation of proteins is a key function of the biosynthetic-secretory pathway in the endoplasmic reticulum (ER) and Golgi apparatus. Glycosylated proteins play a crucial role in cell trafficking and signaling, cell-cell adhesion, blood-group antigenicity, and immune response. In addition, the glycosylation of proteins is an important parameter in the optimization of many glycoprotein-based drugs such as monoclonal antibodies. In vitro glycoengineering of proteins requires glycosyltransferases as well as expensive nucleotide sugars...
September 18, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28919057/adp-dependent-phosphofructokinases-from-the-archaeal-order-methanosarcinales-display-redundant-glucokinase-activity
#2
Ricardo A Zamora, Felipe Gonzalez-Órdenes, Victor Castro-Fernández, Victoria Guixé
The genome of Methanosarcinales organisms presents both ADP-dependent glucokinase and phosphofructokinase genes. However, Methanococcoides burtonii has a truncate glucokinase gene with a large deletion at the C-terminal, where the catalytic GXGD motif is located. Characterization of its phosphofructokinase annotated protein shows that is a bifunctional enzyme able to supply the absence of the glucokinase activity. Moreover, kinetic analyses of the phosphofructokinase annotated enzyme from, Methanohalobium evestigatum demonstrated that this enzyme is also bifunctional...
September 14, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28891310/the-adverse-effects-of-perinatal-exposure-to-nonylphenol-on-carbohydrate-metabolism-in-male-offspring-rats
#3
J Yang, J Yu, P Wang, Y Luo, X F Yang, X S Yang, W M Li, J Xu
BACKGROUND: We sought to investigate the adverse effects of perinatal exposure to nonylphenol (NP) on carbohydrate metabolism of male offspring rats. METHODS: Thirty-two healthy pregnant Sprague Dawley rats were randomly divided into four groups, control normal diet group (C), NP normal diet group (NPN), control high-energy diet group (CH), and NP high-energy diet group (NPH). Both of the control groups were received a gavage of corn oil and the NP-groups were received NP (200 mg/kg/day) from gestational days 6 to post-natal day (PND) 21...
September 11, 2017: International Journal of Environmental Health Research
https://www.readbyqxmd.com/read/28891024/resveratrol-supplementation-improves-lipid-and-glucose-metabolism-in-high-fat-diet-fed-blunt-snout-bream
#4
Dingdong Zhang, Yanan Yan, Hongyan Tian, Guangzhen Jiang, Xiangfei Li, Wenbin Liu
Here, we aimed to investigate whether resveratrol (RSV) can ameliorate high-fat diet (HFD)-induced metabolic disorder in fish. Blunt snout bream (Megalobrama amblycephala) with average weight 27.99 ± 0.56 g were fed a normal fat diet (NFD, 5% fat, w/w), a HFD (11% fat), or a HFD supplemented with 0.04, 0.36, or 1.08% RSV for 10 weeks. As expected, fish fed a HFD developed hepatic steatosis, as shown by elevated hepatic and plasma triglycerides, raised whole body fat, intraperitoneal fat ratio and hepatosomatic index, and increased plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST)...
September 10, 2017: Fish Physiology and Biochemistry
https://www.readbyqxmd.com/read/28880474/%C3%AE-cell-signalling-and-insulin-secretagogues-a-path-for-improved-diabetes-therapy
#5
REVIEW
Susumu Seino, Kenji Sugawara, Norihide Yokoi, Harumi Takahashi
Insulin secretagogues including sulfonylureas, glinides and incretin-related drugs such as dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide-1 receptor agonists are widely used for treatment of type 2 diabetes. In addition, glucokinase activators and G-protein-coupled receptor 40 (GPR40) agonists also have been developed, although the drugs are not clinically usable. These different drugs exert their effects on insulin secretion by different mechanisms. Recent advances in β-cell signalling studies have not only deepened our understanding of insulin secretion but also revealed novel mechanisms of insulin secretagogues...
September 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28867816/dairy-product-consumption-interacts-with-glucokinase-gck-gene-polymorphisms-associated-with-insulin-resistance
#6
Marine S Da Silva, Dominic Chartrand, Marie-Claude Vohl, Olivier Barbier, Iwona Rudkowska
Dairy product intake and a person's genetic background have been reported to be associated with the risk of type 2 diabetes (T2D). The objective of this study was to examine the interaction between dairy products and genes related to T2D on glucose-insulin homeostasis parameters. A validated food frequency questionnaire, fasting blood samples, and glucokinase (GCK) genotypes were analyzed in 210 healthy participants. An interaction between rs1799884 in GCK and dairy intake on the homeostasis model assessment of insulin resistance was identified...
August 30, 2017: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/28843471/should-the-clinical-criteria-for-suspecting-glucokinase-mutation-related-hyperglycemia-mody-2-be-revisited-during-pregnancy
#7
Carl-Hugo Lachance, Michel Baillargeon
No abstract text is available yet for this article.
August 23, 2017: Canadian Journal of Diabetes
https://www.readbyqxmd.com/read/28842611/evidence-based-tailoring-of-bioinformatics-approaches-to-optimize-methods-that-predict-the-effects-of-nonsynonymous-amino-acid-substitutions-in-glucokinase
#8
Daniela Šimčíková, Lucie Kocková, Kateřina Vackářová, Miroslav Těšínský, Petr Heneberg
Computational methods that allow predicting the effects of nonsynonymous substitutions are an integral part of exome studies. Here, we validated and improved their specificity by performing a comprehensive bioinformatics analysis combined with experimental and clinical data on a model of glucokinase (GCK): 8835 putative variations, including 515 disease-associated variations from 1596 families with diagnoses of monogenic diabetes (GCK-MODY) or persistent hyperinsulinemic hypoglycemia of infancy (PHHI), and 126 variations with available or newly reported (19 variations) data on enzyme kinetics...
August 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28810182/selenium-increases-hepatic-dna-methylation-and-modulates-one-carbon-metabolism-in-the-liver-of-mice
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
Anna Wędrychowicz, Ewa Tobór, Magdalena Wilk, Ewa Ziółkowska-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 Southwest Poland and to search for phenotype-genotype correlations. METHODS: We conducted a retrospective analysis of data on 37 CGK-MODY patients consisting of 21 girls and 16 boys of ages 1.9-20.1 (mean 12.5±5.2) years, treated in our centre in the time period between 2002 and 2013. RESULTS: GCK-MODY carriers were found in a frequency of 3% among 1043 diabetes mellitus (DM) patients and constituted the second most numerous group of DM patients, following type 1 DM, in our centre...
September 1, 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
#20
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
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