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Glucokinase

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https://www.readbyqxmd.com/read/28214879/thiamine-deprivation-produces-a-liver-atp-deficit-and-metabolic-and-genomic-effects-in-mice-findings-are-parallel-to-those-of-biotin-deficiency-and-have-implications-for-energy-disorders
#1
Alain de J Hernandez-Vazquez, Josue Andres Garcia-Sanchez, Elizabeth Moreno-Arriola, Ana Salvador-Adriano, Daniel Ortega-Cuellar, Antonio Velazquez-Arellano
Thiamine is one of several essential cofactors for ATP generation. Its deficiency, like in beriberi and in the Wernicke-Korsakoff syndrome, has been studied for many decades. However, its mechanism of action is still not completely understood at the cellular and molecular levels. Since it acts as a coenzyme for dehydrogenases of pyruvate, branched-chain keto acids, and ketoglutarate, its nutritional privation is partly a phenocopy of inborn errors of metabolism, among them maple syrup urine disease. In the present paper, we report metabolic and genomic findings in mice deprived of thiamine...
February 18, 2017: Journal of Nutrigenetics and Nutrigenomics
https://www.readbyqxmd.com/read/28209058/rare-sugar-syrup-containing-d-allulose-but-not-high-fructose-corn-syrup-maintains-glucose-tolerance-and-insulin-sensitivity-partly-via-hepatic-glucokinase-translocation-in-wistar-rats
#2
Tomoya Shintani, Takako Yamada, Noriko Hayashi, Tetsuo Iida, Yasuo Nagata, Nobuaki Ozaki, Yukiyasu Toyoda
Ingestion of high fructose corn syrup (HFCS) is associated with the risk of both diabetes and obesity. Rare sugar syrup (RSS) has been developed by alkaline isomerization of HFCS and has anti-obesity and anti-diabetic effects. However, the influence of RSS on glucose metabolism has not been explored. We investigated whether long-term administration of RSS maintains glucose tolerance and whether the underlying mechanism involves hepatic glucokinase translocation. Wistar rats were administered water, RSS, or HFCS in drinking water for 10 weeks, and then evaluated for glucose tolerance, insulin tolerance, liver glycogen content, and subcellular distribution of liver glucokinase...
February 16, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28207836/tmg-123-a-novel-glucokinase-activator-exerts-durable-effects-on-hyperglycemia-without-increasing-triglyceride-in-diabetic-animal-models
#3
Yoshinori Tsumura, Yu Tsushima, Azusa Tamura, Makiko Hasebe, Masanobu Kanou, Hirotsugu Kato, Tsunefumi Kobayashi
Glucokinase (GK) plays a critical role for maintaining glucose homeostasis with regulating glucose uptake in liver and insulin secretion in pancreas. GK activators have been reported to decrease blood glucose levels in patients with type 2 diabetes mellitus. However, clinical development of GK activators has failed due to the loss of glucose-lowering effects and increased plasma triglyceride levels after chronic treatment. Here, we generated a novel GK activator, TMG-123, examined its in vitro and in vivo pharmacological characteristics, and evaluated its risks of aforementioned clinical issues...
2017: PloS One
https://www.readbyqxmd.com/read/28206714/opposite-effects-of-a-glucokinase-activator-and-metformin-on-glucose-regulated-gene-expression-in-hepatocytes
#4
Ziad H Al-Oanzi, Sophia Fountana, Tabassum Moonira, Susan J Tudhope, John L Petrie, Ahmed Alshawi, Gillian Patman, Catherine Arden, Helen L Reeves, Loranne Agius
AIM: Small molecule activators of glucokinase (GKAs) have been extensively explored as potential anti-hyperglycaemic drugs for type 2 diabetes (T2D). Several GKAs were remarkably effective at lowering blood glucose during early therapy but then lost their glycaemic efficacy chronically during clinical trials. We used rat hepatocytes to test the hypothesis that GKAs raise hepatocyte glucose 6-phosphate, (G6P, the glucokinase product) and down-stream metabolites with consequent repression of the liver glucokinase gene (Gck)...
February 16, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28192880/ameliorating-effect-of-betanin-a-natural-chromoalkaloid-by-modulating-hepatic-carbohydrate-metabolic-enzyme-activities-and-glycogen-content-in-streptozotocin-nicotinamide-induced-experimental-rats
#5
Indumathi Dhananjayan, Sujithra Kathiroli, Srinivasan Subramani, Vinothkumar Veerasamy
Betanin, a chromoalkaloid of beetroot, has shown significant biological effects of antioxidants, anti-inflammatory and anticarcinogenic activities. So, we attempted to determine whether betanin (a natural pigment) would be protective against hyperglycemia in streptozotocin (STZ) - nicotinamide (NA) induced diabetic rats. Rats were injected with STZ (40mg/kgb.w.) 15 mins after the administration of NA (110mg/kgb.w.) by intraperitonially (i.p.) 30days for the induction of experimental diabetes mellitus. After 72h diabetic rats were treated with betanin orally at a doses of 10, 20 and 40mg/kg b...
February 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28191470/effects-of-a-novel-glucokinase-activator-hms5552-on-glucose-metabolism-in-a-rat-model-of-type-2-diabetes-mellitus
#6
Ping Wang, Huili Liu, Li Chen, Yingli Duan, Qunli Chen, Shoumin Xi
Glucokinase (GK) plays a critical role in the control of whole-body glucose homeostasis. We investigated the possible effects of a novel glucokinase activator (GKA), HMS5552, to the GK in rats with type 2 diabetes mellitus (T2DM). Male Sprague-Dawley (SD) rats were divided into four groups: control group, diabetic group, low-dose (10 mg/kg) HMS5552-treated diabetic group (HMS-L), and high-dose (30 mg/kg) HMS5552-treated diabetic group (HMS-H). HMS5552 was administered intragastrically to the T2DM rats for one month...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28182770/biochemical-and-biophysical-investigations-of-the-interaction-between-human-glucokinase-and-pro-apoptotic-bad
#7
Alix Rexford, Diego A R Zorio, Brian G Miller
The glycolytic enzyme glucokinase (GCK) and the pro-apoptotic protein BAD reportedly reside within a five-membered complex that localizes to the mitochondria of mammalian hepatocytes and pancreatic β-cells. Photochemical crosslinking studies using a synthetic analog of BAD's BH3 domain and in vitro transcription/translation experiments support a direct interaction between BAD and GCK. To investigate the biochemical and biophysical consequences of the BAD:GCK interaction, we developed a method for the production of recombinant human BAD...
2017: PloS One
https://www.readbyqxmd.com/read/28163940/asymptomatic-congenital-hyperinsulinism-due-to-a-glucokinase-activating-mutation-treated-as-adrenal-insufficiency-for-twelve-years
#8
Kae Morishita, Chika Kyo, Takako Yonemoto, Rieko Kosugi, Tatsuo Ogawa, Tatsuhide Inoue
Congenital hyperinsulinism (CHI) caused by a glucokinase- (GCK-) activating mutation shows autosomal dominant inheritance, and its severity ranges from mild to severe. A 43-year-old female with asymptomatic hypoglycemia (47 mg/dL) was diagnosed as partial adrenal insufficiency and the administration of hydrocortisone (10 mg/day) was initiated. Twelve years later, her 8-month-old grandchild was diagnosed with CHI. Heterozygosity of exon 6 c.590T>C (p.M197T) was identified in a gene analysis of GCK, which was also detected in her son and herself...
2017: Case Reports in Endocrinology
https://www.readbyqxmd.com/read/28122818/effects-of-g6pc2-deletion-on-body-weight-and-cholesterol-in-mice
#9
Kayla A Boortz, Kristen E Syring, Lynley D Pound, Huan Mo, Lisa Bastarache, James K Oeser, Owen Patrick McGuinness, Joshua C Denny, Richard O'Brien
Genome wide association study (GWAS) data have linked the G6PC2 gene to variations in fasting blood glucose (FBG). G6PC2 encodes an islet-specific glucose-6-phosphatase catalytic subunit that forms a substrate cycle with the beta cell glucose sensor glucokinase. This cycle modulates the glucose sensitivity of insulin secretion and hence FBG. GWAS data have not linked G6PC2 to variations in body weight but we previously reported that female C57BL/6J G6pc2 knockout (KO) mice were lighter than wild-type littermates on both a chow and high fat diet...
January 25, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28118753/protective-effects-of-leucine-on-redox-status-and-mitochondrial-related-gene-abundance-in-the-jejunum-of-intrauterine-growth-retarded-piglets-during-early-weaning-period
#10
Qiang Huang, Wen Xu, Kai-Wen Bai, Jin-Tian He, Hussain Ahmad, Le Zhou, Li-Li Zhang, Tian Wang
The aim of this study was to investigate the effects of dietary supplementation with 0.35% l-leucine on redox status and gene abundance relating to mitochondrial biogenesis and function in the jejunum of intrauterine growth-retarded (IUGR) piglets during early weaning period. According to a 2 × 2 factorial arrangement, 16 IUGR and 16 normal body weight (NBW) piglets were fed a basal diet without l-leucine supplementation or a basal diet plus 0.35% l-leucine supplementation from the age of 14 to 35 d. The results showed that compared with NBW piglets, IUGR piglets had a lower (p < 0...
January 24, 2017: Archives of Animal Nutrition
https://www.readbyqxmd.com/read/28116849/a-pharmacological-approach-to-understanding-the-control-of-insulin-secretion-in-human-islets
#11
Jean-Claude Henquin, Denis Dufrane, Valery Gmyr, Julie Kerr-Conte, Myriam Nenquin
AIMS: To understand better the control of insulin secretion (IS) by human β-cells and identify similarities and differences with rodent models. METHODS: Dynamic IS was measured in perifused human islets treated with pharmacological agents of known modes of action. RESULTS: Glucokinase activation (Ro28-1675) lowered the glucose threshold for stimulation of IS to 1 mmol/l (G1), augmented the response to G3-G5 but not to G8-G15 whereas tolbutamide remained active in G20, which indicates that not all KATP -channels were closed by high glucose...
January 24, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28094769/ipsc-derived-%C3%AE-cells-model-diabetes-due-to-glucokinase-deficiency
#12
Haiqing Hua, Linshan Shang, Hector Martinez, Matthew Freeby, Mary Pat Gallagher, Thomas Ludwig, Liyong Deng, Ellen Greenberg, Charles LeDuc, Wendy K Chung, Robin Goland, Rudolph L Leibel, Dieter Egli
No abstract text is available yet for this article.
January 17, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28073120/nano-pelargonidin-protects-hyperglycemic-induced-l6-cells-against-mitochondrial-dysfunction
#13
Asmita Samadder, Debojyoti Tarafdar, Suresh K Abraham, Kumaresh Ghosh, Anisur Rahman Khuda-Bukhsh
Nano-encapsulation of several natural products has become an important tool in enhancing the bioavailability of some modern drugs against many diseases. Pelargonidin is an anthocyanidin found in many fruits and vegetables. Pelargonidin is loaded with poly-lactide-co-glycolic-acid, a non-toxic biodegradable polymer, to produce nano-pelargonidin. Size, morphology, zeta potential, and planar uniformity of formulated nano-pelargonidin were determined by atomic force microscopy and dynamic light scattering. The time required for cellular entry, folds of nano-pelargonidin, and drug encapsulation efficiency of poly-lactide-co-glycolic-acid were also ascertained...
January 10, 2017: Planta Medica
https://www.readbyqxmd.com/read/28012402/maturity-onset-diabetes-of-the-young-mody-in-brazil-establishment-of-a-national-registry-and-appraisal-of-available-genetic-and-clinical-data
#14
Fernando M A Giuffrida, Regina S Moises, Leticia S Weinert, Luis E Calliari, Thais Della Manna, Renata P Dotto, Luciana F Franco, Lilian A Caetano, Milena G Teles, Renata Andrade Lima, Crésio Alves, Sergio A Dib, Sandra P Silveiro, Magnus R Dias-da-Silva, Andre F Reis
AIMS: Maturity-Onset Diabetes of the Young (MODY) comprises a heterogeneous group of monogenic forms of diabetes caused by mutations in at least 14 genes, but mostly by mutations in Glucokinase (GCK) and hepatocyte nuclear factor-1 homeobox A (HNF1A). This study aims to establish a national registry of MODY cases in Brazilian patients, assessing published and unpublished data. METHODS: 311 patients with clinical characteristics of MODY were analyzed, with unpublished data on 298 individuals described in 12 previous publications and 13 newly described cases in this report...
January 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28000102/translational-modeling-and-simulation-in-supporting-early-phase-clinical-development-of-new-drug-a-learn-research-confirm-process
#15
Dongyang Liu, Yi Zhang, Ji Jiang, John Choi, Xuening Li, Dalong Zhu, Dawei Xiao, Yanhua Ding, Hongwei Fan, Li Chen, Pei Hu
BACKGROUND AND OBJECTIVE: Pharmacokinetic/pharmacodynamic modeling and simulation can aid clinical drug development by dynamically integrating key system- and drug-specific information into predictive profiles. In this study, we propose a methodology to predict pharmacokinetic/pharmacodynamic profiles of sinogliatin (HMS-5552, RO-5305552), a novel glucokinase activator to treat diabetes mellitus, for first-in-patient (FIP) studies. METHODS AND RESULTS: Initially, pharmacokinetic/pharmacodynamic profiles of sinogliatin and another glucokinase activator (US2) previously acquired from healthy subjects were fitted using Model A incorporating an indirect response mechanism...
December 20, 2016: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/27943105/hypolipidemic-and-hypoglycemic-activities-of-a-oleanolic-acid-derivative-from-malva-parviflora-on-streptozotocin-induced-diabetic-mice
#16
Rosa Martha Pérez Gutiérrez
One new oleanolic acid derivative, 2α,3β,23α,29α tetrahydroxyolean-12(13)-en-28-oic acid (1) was isolated from the aerial parts of Malva parviflora. Their structure was characterized by spectroscopic methods. The hypolipidemic and hypoglycemic activities of 1 was analyzed in in streptozotocin (STZ)-nicotinamide-induced type 2 diabetes in mice (MD) and type 1 diabetes in streptozotocin-induced diabetic mice (SD). Triterpene was administered orally at doses of 20 mg/kg for 4 weeks. Organ weight, body weight, glucose, fasting insulin, cholesterol-related lipid profile parameters, glutamate oxaloacetate transaminase (SGOT), glutamate pyruvate transaminase (SGPT), serum alkaline phosphatase (SALP), glucokinase, hexokinase, glucose-6-phosphatase activities and glycogen in liver were measured after 4 weeks of treatment...
December 10, 2016: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/27935851/an-analysis-of-the-sequence-of-the-bad-gene-among-patients-with-maturity-onset-diabetes-of-the-young-mody
#17
Karolina Antosik, Piotr Gnyś, Przemysława Jarosz-Chobot, Małgorzata Myśliwiec, Agnieszka Szadkowska, Maciej Małecki, Wojciech Młynarski, Maciej Borowiec
BACKGROUND: Monogenic diabetes is a rare disease caused by single gene mutations. Maturity onset diabetes of the young (MODY) is one of the major forms of monogenic diabetes recognised in the paediatric population. To date, 13 genes have been related to MODY development. The aim of the study was to analyse the sequence of the BCL2-associated agonist of cell death (BAD) gene in patients with clinical suspicion of GCK-MODY, but who were negative for glucokinase (GCK) gene mutations. METHODS: A group of 122 diabetic patients were recruited from the "Polish Registry for Paediatric and Adolescent Diabetes - nationwide genetic screening for monogenic diabetes" project...
January 1, 2017: Journal of Pediatric Endocrinology & Metabolism: JPEM
https://www.readbyqxmd.com/read/27925195/palmitoleic-acid-improves-metabolic-functions-in-fatty-liver-by-ppar%C3%AE-dependent-ampk-activation
#18
Camila O Souza, Alexandre A S Teixeira, Luana A Biondo, Edson A Lima, Helena A P Batatinha, Jose C Rosa Neto
BACKGROUND: Palmitoleic acid, since described as lipokine, increases glucose uptake by modulation of 5'AMP-activated protein kinase (AMPK), as well as increasing lipolysis by activation of peroxisome proliferator-activated receptor-α (PPARα), in adipose tissue. However in liver, the effects of palmitoleic acid on glucose metabolism and the role of PPARα remain unknown. OBJECTIVE: To investigate whether palmitoleic acid improved the hepatic insulin sensitivity of obese mice...
December 7, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27918882/metabolic-engineering-of-corynebacterium-glutamicum-for-the-production-of-3-hydroxypropionic-acid-from-glucose-and-xylose
#19
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 glutamicum was 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 of gpd and gpp from Saccharomyces cerevisiae) and 3-HP production (pduCDEGH from Klebsiella pneumoniae and aldehyde dehydrogenases from various resources)...
January 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/27915410/the-properties-and-potential-metabolic-role-of-glucokinase-in-halotolerant-obligate-methanotroph-methylomicrobium-alcaliphilum-20z
#20
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
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