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Glucokinase

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https://www.readbyqxmd.com/read/27918882/metabolic-engineering-of-corynebacterium-glutamicum-for-the-production-of-3-hydroxypropionic-acid-from-glucose-and-xylose
#1
Zhen Chen, Jinhai Huang, Yao Wu, Wenjun Wu, Ye Zhang, Dehua Liu
3-Hydroxypropionic acid (3-HP) is a promising platform chemical which can be used for the production of various value-added chemicals. In this study,Corynebacterium glutamicumwas metabolically engineered to efficiently produce 3-HP from glucose and xylose via the glycerol pathway. A functional 3-HP synthesis pathway was engineered through a combination of genes involved in glycerol synthesis (fusion ofgpdandgppfromSaccharomyces cerevisiae) and 3-HP production (pduCDEGHfromKlebsiella pneumoniaeand aldehyde dehydrogenases from various resources)...
December 2, 2016: Metabolic Engineering
https://www.readbyqxmd.com/read/27915410/the-properties-and-potential-metabolic-role-of-glucokinase-in-halotolerant-obligate-methanotroph-methylomicrobium-alcaliphilum-20z
#2
Ildar I Mustakhimov, Olga N Rozova, Natalia P Solntseva, Valentina N Khmelenina, Alexander S Reshetnikov, Yuri A Trotsenko
Aerobic bacteria utilizing methane as the carbon and energy source do not use sugars as growth substrates but possess the gene coding for glucokinase (Glk), an enzyme converting glucose into glucose 6-phosphate. Here we demonstrate the functionality and properties of Glk from an obligate methanotroph Methylomicrobium alcaliphilum 20Z. The recombinant Glk obtained by heterologous expression in Escherichia coli was found to be close in biochemical properties to other prokaryotic Glks. The homodimeric enzyme (2 × 35 kDa) catalyzed ATP-dependent phosphorylation of glucose and glucosamine with nearly equal activity, being inhibited by ADP (K i = 2...
December 3, 2016: Antonie Van Leeuwenhoek
https://www.readbyqxmd.com/read/27893760/leaf-extract-from-lithocarpus-polystachyus-rehd-promote-glycogen-synthesis-in-t2dm-mice
#3
Jinfei Wang, Yumin Huang, Kaixiang Li, Yingying Chen, Diana Vanegas, Eric Scott McLamore, Yingbai Shen
The purpose of this study was to investigate the effects of leaf extract from Lithocarpus polystachyus Rehd. on type II diabetes mellitus (T2DM) and the active ingredients of this effect. In addition, this study determined, for the first time, the underlying molecular and pharmacological mechanisms of the extracts on hyperglycemia using long-term double high diet-fed and streptozotocin (STZ) induced type II diabetic mice. In the present study, leaf extract, phloridzin and trilobatin were assessed in vivo (gavage) and in vitro (non-invasive micro-test technique, NMT) in experimental T2DM mice...
2016: PloS One
https://www.readbyqxmd.com/read/27886975/in-vitro-metabolic-engineering-of-bioelectricity-generation-by-the-complete-oxidation-of-glucose
#4
Zhiguang Zhu, Y-H Percival Zhang
The direct generation of electricity from the most abundant renewable sugar, glucose, is an appealing alternative to the production of liquid biofuels and biohydrogen. However, enzyme-catalyzed bioelectricity generation from glucose suffers from low yields due to the incomplete oxidation of the six-carbon compound glucose via one or few enzymes. Here, we demonstrate a synthetic ATP- and CoA-free 12-enzyme pathway to implement the complete oxidation of glucose in vitro. This pathway is comprised of glucose phosphorylation via polyphosphate glucokinase, NADH generation catalyzed by glucose 6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6PGDH), electron transfer from NADH to the anode, and glucose 6-phosphate regeneration via the non-oxidative pentose phosphate pathway and gluconeogenesis...
November 23, 2016: Metabolic Engineering
https://www.readbyqxmd.com/read/27882918/hyperglycaemia-induces-metabolic-dysfunction-and-glycogen-accumulation-in-pancreatic-%C3%AE-cells
#5
Melissa F Brereton, Maria Rohm, Kenju Shimomura, Christian Holland, Sharona Tornovsky-Babeay, Daniela Dadon, Michaela Iberl, Margarita V Chibalina, Sheena Lee, Benjamin Glaser, Yuval Dor, Patrik Rorsman, Anne Clark, Frances M Ashcroft
Insulin secretion from pancreatic β-cells is impaired in all forms of diabetes. The resultant hyperglycaemia has deleterious effects on many tissues, including β-cells. Here we show that chronic hyperglycaemia impairs glucose metabolism and alters expression of metabolic genes in pancreatic islets. In a mouse model of human neonatal diabetes, hyperglycaemia results in marked glycogen accumulation, and increased apoptosis in β-cells. Sulphonylurea therapy rapidly normalizes blood glucose levels, dissipates glycogen stores, increases autophagy and restores β-cell metabolism...
November 24, 2016: Nature Communications
https://www.readbyqxmd.com/read/27870481/glycemic-effect-and-safety-of-a-systemic-partial-glucokinase-activator-pf-04937319-in-patients-with-type-2-diabetes-mellitus-inadequately-controlled-on-metformin-a-randomized-crossover-active-controlled-study
#6
William S Denney, Douglas S Denham, Michael R Riggs, Neeta B Amin
Glucokinase enhances glucose conversion to glucose-6-phosphate, causing glucose-stimulated insulin secretion from pancreatic β cells and increased hepatic glucose uptake. PF-04937319 is a partial glucokinase activator designed to maintain efficacy with reduced hypoglycemia risk. In this randomized, double-blind, double-dummy, 3-period crossover phase 1b study, patients aged 18-70 years with type 2 diabetes mellitus and on metformin received once-daily PF-04937319 (300 mg), split-dose PF-04937319 (150+100 mg; breakfast+lunch), or sitagliptin (100 mg once daily)...
November 2016: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/27861733/multiplex-growth-rate-phenotyping-of-synthetic-mutants-in-selection-to-engineer-glucose-and-xylose-co-utilization-in-escherichia-coli
#7
A J Groot, S C Cepress-Mclean, A Robbins-Pianka, R Knight, R T Gill
Engineering the simultaneous consumption of glucose and xylose sugars is critical to enable the sustainable production of biofuels from cellulosic biomass. In most major industrial microorganisms glucose completely inhibits the uptake of xylose, limiting efficient sugar mixture conversion. In E.coli removal of the major glucose transporter PTS allows for glucose and xylose co-consumption but only after prolonged adaptation, which is an effective process but hard to control and prone to co-evolving undesired traits...
November 14, 2016: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/27852188/a-review-of-maturity-onset-diabetes-of-the-young-mody-and-challenges-in-the-management-of-glucokinase-mody
#8
Ramy H Bishay, Jerry R Greenfield
Maturity onset diabetes of the young (MODY), the most common monogenic form of diabetes, accounts for 1-2% of all diabetes diagnoses. Glucokinase (GCK)-MODY (also referred to as MODY2) constitutes 10-60% of all MODY cases and is inherited as an autosomal dominant heterozygous mutation, resulting in loss of function of the GCK gene. Patients with GCK-MODY generally have mild, fasting hyperglycaemia that is present from birth, are commonly leaner and diagnosed at a younger age than patients with type 2 diabetes, and rarely develop complications from diabetes...
November 21, 2016: Medical Journal of Australia
https://www.readbyqxmd.com/read/27836638/maternal-bisphenol-a-exposure-alters-rat-offspring-hepatic-and-skeletal-muscle-insulin-signaling-protein-abundance
#9
Kristina D Galyon, Farnoosh Farshidi, Guang Han, Michael G Ross, Mina Desai, Juanita K Jellyman
BACKGROUND: The obesogenic and diabetogenic effects of the environmental toxin bisphenol A during critical windows of development are well recognized. Liver and skeletal muscle play a central role in the control of glucose production, utilization, and storage. OBJECTIVES: We hypothesized that maternal bisphenol A exposure disrupts insulin signaling in rat offspring liver and skeletal muscle. We determined the protein expression of hepatic and skeletal muscle insulin signaling molecules including insulin receptor beta, its downstream target insulin receptor substrate 1 and glucose transporters (glucose transporter 2, glucose transporter 4), and hepatic glucose-regulating enzymes phosphoenolpyruvate carboxykinase and glucokinase...
November 9, 2016: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/27823935/glucose-enhances-rat-islet-function-via-stimulating-cart-expression
#10
Wan Xu, Yuqing Zhang, Mengyao Bai, Feiye Zhou, Ruyuan Deng, Xueying Ji, Juan Zhang, Yun Liu, Libin Zhou, Xiao Wang
Cocaine- and amphetamine-regulated transcript (CART) is an anorexigenic peptide widely expressed in the central and peripheral nervous systems, as well as in endocrine cells. CART is markedly upregulated in the β-cells of several rodent models of type-2 diabetes. The stimulatory effect of exogenous CART peptide on insulin secretion is cAMP dependent. Glucose is the most important regulator of islet function. However, the role of CART in glucose-potentiated insulin secretion remains unclear. Here, our results showed that glucose time- and dose-dependently elicited CART mRNA expression in rat islets...
December 2, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27809830/the-ethyl-acetate-fraction-of-corn-silk-exhibits-dual-antioxidant-and-anti-glycation-activities-and-protects-insulin-secreting-cells-from-glucotoxicity
#11
Chia-Chuan Chang, Wei Yuan, Hsiao-Yuh Roan, Jia-Ling Chang, Hsiu-Chen Huang, Yu-Ching Lee, Huey Jen Tsay, Hui-Kang Liu
BACKGROUND: In this study, we aimed to develop a Stigmata Maydis (corn silk) fraction with dual bio-activities against oxidative stress and protein glycation to protect β-cells from diabetes-induced failure. METHODS: Corn silk fractions were prepared by partition and chemically characterised by thin-layer chromatography. Free radical scavenging assay, glycation assay, and cell-based viability test (neutral red) were employed to decide the best fraction. Cell death analysis was executed by annexin V/ Propidium iodide staining...
November 3, 2016: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/27802864/glucokinase-mutation-a-rare-cause-of-recurrent-hypoglycemia-in-adults-a-case-report-and-literature-review
#12
Oluremi N Ajala, David M Huffman, Ibrahim I Ghobrial
BACKGROUND: Hypoglycemia occurs frequently in patients both in the inpatient and outpatient settings. While most hypoglycemia unrelated to diabetes treatment results from excessive endogenous insulin action, rare cases involve functional and congenital mutations in glycolytic enzymes of insulin regulation. CASE: A 21-year-old obese woman presented to the emergency department with complaints of repeated episodes of lethargy, syncope, dizziness, and sweating. She was referred from an outside facility on suspicion of insulinoma, with severe hypoglycemia unresponsive to repeated dextrose infusions...
2016: Journal of Community Hospital Internal Medicine Perspectives
https://www.readbyqxmd.com/read/27802600/comparison-of-regulation-mechanisms-of-five-mulberry-ingredients-on-insulin-secretion-under-oxidative-stress
#13
Yun-Chong Zheng, Hao He, Xing Wei, Sheng Ge, Yan-Hua Lu
The effects of mulberry ingredients including 1-deoxynojrimycin (DNJ), resveratrol (RES), oxyresveratrol (OXY), cyanidin-3-glucoside (C3G), and cyanidin-3-rutinoside (C3R) on insulin secretion under oxidative stress were investigated. The results revealed that they had distinct effects on insulin secretion in H2O2-induced MIN 6 cells, especially DNJ, C3G and C3R, While RES and OXY showed modest effects in low dose (12.5μM). The mechanisms were demonstrated in signal pathway that after treatment with DNJ, C3G and C3R, the expressions of glucokinase (GK) were up-regulated, leading to intracellular ATP accumulation and insulin secretion...
November 1, 2016: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/27786288/an-inhibitor-of-fibroblast-growth-factor-receptor-1-fgfr1-promotes-late-stage-terminal-differentiation-from-ngn3-pancreatic-endocrine-progenitors
#14
Yzumi Yamashita-Sugahara, Masahito Matsumoto, Manami Ohtaka, Ken Nishimura, Mahito Nakanishi, Kohnosuke Mitani, Yasushi Okazaki
Human induced pluripotent stem cells (hiPSCs) provide a potential resource for regenerative medicine. To identify the signalling pathway(s) contributing to the development of functional β cells, we established a tracing model consisting of dual knock-in hiPSCs (INS-Venus/NGN3-mCherry) (hIveNry) expressing the fluorescent proteins Venus and mCherry under the control of intrinsic insulin (INS) and neurogenin 3 (NGN3) promoters, respectively. hIveNry iPSCs differentiated into NGN3- and mCherry-positive endocrine progenitors and then into Venus-positive β cells expressing INS, PDX1, NKX6...
October 27, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27774459/hyperglycemia-induced-by-glucokinase-deficiency-accelerates-atherosclerosis-development-and-impairs-lesion-regression-in-combined-heterozygous-glucokinase-and-the-apolipoprotein-e-knockout-mice
#15
Damilola D Adingupu, Suvi E Heinonen, Anne-Christine Andréasson, Mikael Brusberg, Andrea Ahnmark, Margareta Behrendt, Brendan Leighton, Ann-Cathrine Jönsson-Rylander
Aim. Models combining diabetes and atherosclerosis are important in evaluating the cardiovascular (CV) effects and safety of antidiabetes drugs in the development of treatments targeting CV complications. Our aim was to evaluate if crossing the heterozygous glucokinase knockout mouse (GK(+/-)) and hyperlipidemic mouse deficient in apolipoprotein E (ApoE(-/-)) will generate a disease model exhibiting a diabetic and macrovascular phenotype. Methods. The effects of defective glucokinase on the glucose metabolism and on the progression and regression of atherosclerosis on high-fat diets were studied in both genders of GK(+/-)ApoE(-/-) and ApoE(-/-) mice...
2016: Journal of Diabetes Research
https://www.readbyqxmd.com/read/27707936/liver-glucose-metabolism-in-humans
#16
REVIEW
María M Adeva-Andany, Noemi Pérez-Felpete, Carlos Fernández-Fernández, Cristóbal Donapetry-García, Cristina Pazos-García
Information about normal hepatic glucose metabolism may help to understand pathogenic mechanisms underlying obesity and diabetes mellitus. In addition, liver glucose metabolism is involved in glycosylation reactions and connected with fatty acid metabolism. The liver receives dietary carbohydrates directly from the intestine via the portal vein. Glucokinase phosphorylates glucose to glucose 6-phosphate inside the hepatocyte, ensuring that an adequate flow of glucose enters the cell to be metabolized. Glucose 6-phosphate may proceed to several metabolic pathways...
December 2016: Bioscience Reports
https://www.readbyqxmd.com/read/27704066/the-potential-beneficial-effects-of-phenolic-compounds-isolated-from-a-pilosa-ledeb-on-insulin-resistant-hepatic-hepg2-cells
#17
Hui Teng, Lei Chen, Hongbo Song
Agrimonia pilosa Ledeb (AP) has already been applied in practice for the treatment of different disorders and is available to access without the provision of a medical prescription. The present study aims at investigating the effect of bioactive compounds isolated from AP on the improvement of insulin resistance, figuring out the mechanism in insulin-responsive cell lines. Five compounds were isolated from AP using column chromatography, including agrimonolide (K1), desmethylagrimonolide (K2), tormentic acid (K3), ursolic acid (K4), and quercetin (K5)...
October 12, 2016: Food & Function
https://www.readbyqxmd.com/read/27695030/phosphorylation-of-staphylococcus-aureus-protein-tyrosine-kinase-affects-the-function-of-glucokinase-and-biofilm-formation
#18
Dudipeta Vasu, Pasupuleti Santhosh Kumar, Uppu Venkateswara Prasad, Vimjam Swarupa, Sthanikam Yeswanth, Lokanathan Srikanth, Manne Mudhu Sunitha, Abhijith Choudhary, Potukuchi Venkata Gurunadha Krishna Sarma
BACKGROUND: When Staphylococcus aureus is grown in the presence of high concentration of external glucose, this sugar is phosphorylated by glucokinase (glkA) to form glucose-6-phosphate. This product subsequently enters into anabolic phase, which favors biofilm formation. The presence of ROK (repressor protein, open reading frame, sugar kinase) motif, phosphate-1 and -2 sites, and tyrosine kinase sites in glkA of S. aureus indicates that phosphorylation must regulate the glkA activity...
October 1, 2016: Iranian Biomedical Journal
https://www.readbyqxmd.com/read/27693527/effect-of-hfd-stz-on-expression-of-genes-involved-in-lipid-cholesterol-and-glucose-metabolism-in-rats
#19
Luisa Pozzo, Andrea Vornoli, Ilaria Coppola, Clara Maria Della Croce, Lucia Giorgetti, Pier Giovanni Gervasi, Vincenzo Longo
AIMS: The aim of the study was to evaluate lipid, cholesterol and glucose metabolism in a novel rat model of non-alcoholic fatty liver disease (NAFLD). MAIN METHODS: Rats (Wistar) were fed high fat/cholesterol diet (HFD) and a single low dose (35mg/kg) of streptozotocin (STZ). Collagen and glycogen content, oxidative stress and glucokinase activity were measured using biochemical assays. Other metabolic pathway were assessed by qRT-PCR. KEY FINDINGS: HFD/STZ treated rats, compared to control ones, showed an increase in expression of biomarkers of inflammation (TNFα, IL6), fibrosis (TGFβ), mitochondrial stress (UCP2) and oxidative stress (GSH and carbonylated proteins) but not of ER stress (CHOP, XBP1)...
September 28, 2016: Life Sciences
https://www.readbyqxmd.com/read/27692165/in-type-1-diabetics-high-dose-biotin-may-compensate-for-low-hepatic-insulin-exposure-promoting-a-more-normal-expression-of-glycolytic-and-gluconeogenic-enyzymes-and-thereby-aiding-glycemic-control
#20
Mark F McCarty
In type 1 diabetics, hepatic exposure to insulin is chronically subnormal even in the context of insulin therapy; as a result, expression of glycolytic enzymes is decreased, and that of gluconeogenic enzymes is enhanced, resulting in a physiologically inappropriate elevation of hepatic glucose output. Subnormal expression of glucokinase (GK) is of particular importance in this regard. Possible strategies for correcting this perturbation of hepatic enzyme expression include administration of small molecule allosteric activators of GK, as well as a procedure known as chronic intermittent intravenous insulin therapy (CIIIT); however, side effects accompany the use of GK activators, and CIIIT is time and labor intensive...
October 2016: Medical Hypotheses
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