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https://www.readbyqxmd.com/read/28934129/a-comprehensive-survey-of-the-roles-of-highly-disordered-proteins-in-type-2-diabetes
#1
Zhihua Du, Vladimir N Uversky
Type 2 diabetes mellitus (T2DM) is a chronic and progressive disease that is strongly associated with hyperglycemia (high blood sugar) related to either insulin resistance or insufficient insulin production. Among the various molecular events and players implicated in the manifestation and development of diabetes mellitus, proteins play several important roles. The Kyoto Encyclopedia of Genes and Genomes (KEGG) database has information on 34 human proteins experimentally shown to be related to the T2DM pathogenesis...
September 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28922661/lysophosphatidic-acid-inhibits-insulin-signaling-in-primary-rat-hepatocytes-via-the-lpa3-receptor-subtype-and-is-increased-in-obesity
#2
Susann Fayyaz, Lukasz Japtok, Fabian Schumacher, Dominik Wigger, Tim Julius Schulz, Kathrin Haubold, Erich Gulbins, Heinz Völler, Burkhard Kleuser
BACKGROUND/AIMS: Obesity is a main risk factor for the development of hepatic insulin resistance and it is accompanied by adipocyte hypertrophy and an elevated expression of different adipokines such as autotaxin (ATX). ATX converts lysophosphatidylcholine to lysophosphatidic acid (LPA) and acts as the main producer of extracellular LPA. This bioactive lipid regulates a broad range of physiological and pathological responses by activation of LPA receptors (LPA1-6). METHODS: The activation of phosphatidylinositide 3-kinases (PI3K) signaling (Akt and GSK-3ß) was analyzed via western blotting in primary rat hepatocytes...
September 1, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28905132/transethnic-insight-into-the-genetics-of-glycaemic-traits-fine-mapping-results-from-the-population-architecture-using-genomics-and-epidemiology-page-consortium
#3
Stephanie A Bien, James S Pankow, Jeffrey Haessler, Yinchang N Lu, Nathan Pankratz, Rebecca R Rohde, Alfred Tamuno, Christopher S Carlson, Fredrick R Schumacher, Petra Bůžková, Martha L Daviglus, Unhee Lim, Myriam Fornage, Lindsay Fernandez-Rhodes, Larissa Avilés-Santa, Steven Buyske, Myron D Gross, Mariaelisa Graff, Carmen R Isasi, Lewis H Kuller, JoAnn E Manson, Tara C Matise, Ross L Prentice, Lynne R Wilkens, Sachiko Yoneyama, Ruth J F Loos, Lucia A Hindorff, Loic Le Marchand, Kari E North, Christopher A Haiman, Ulrike Peters, Charles Kooperberg
AIMS/HYPOTHESIS: Elevated levels of fasting glucose and fasting insulin in non-diabetic individuals are markers of dysregulation of glucose metabolism and are strong risk factors for type 2 diabetes. Genome-wide association studies have discovered over 50 SNPs associated with these traits. Most of these loci were discovered in European populations and have not been tested in a well-powered multi-ethnic study. We hypothesised that a large, ancestrally diverse, fine-mapping genetic study of glycaemic traits would identify novel and population-specific associations that were previously undetectable by European-centric studies...
September 13, 2017: Diabetologia
https://www.readbyqxmd.com/read/28891310/the-adverse-effects-of-perinatal-exposure-to-nonylphenol-on-carbohydrate-metabolism-in-male-offspring-rats
#4
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
#5
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/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/28862987/mody-in-ukraine-genes-clinical-phenotypes-and-treatment
#7
Evgenia Globa, Nataliya Zelinska, Lenka Elblova, Petra Dusatkova, Ondrej Cinek, Jan Lebl, Kevin Colclough, Sian Ellard, Stepanka Pruhova
BACKGROUND: Maturity-onset diabetes of the young (MODY) has not been previously studied in Ukraine. We investigated the genetic etiology in a selected cohort of patients with diabetes diagnosed before 18 years of age, and in their family members. METHODS: Genetic testing of the most prevalent MODY genes (GCK, HNF1A, HNF4A, HNF1B and INS) was undertaken for 36 families (39 affected individuals) by Sanger or targeted next generation sequencing. RESULTS: A genetic diagnosis of MODY was made in 15/39 affected individuals from 12/36 families (33%)...
September 1, 2017: Journal of Pediatric Endocrinology & Metabolism: JPEM
https://www.readbyqxmd.com/read/28855921/diagnosis-and-treatment-of-hyperinsulinaemic-hypoglycaemia-and-its-implications-for-paediatric-endocrinology
#8
REVIEW
Huseyin Demirbilek, Sofia A Rahman, Gonul Gulal Buyukyilmaz, Khalid Hussain
Glucose homeostasis requires appropriate and synchronous coordination of metabolic events and hormonal activities to keep plasma glucose concentrations in a narrow range of 3.5-5.5 mmol/L. Insulin, the only glucose lowering hormone secreted from pancreatic β-cells, plays the key role in glucose homeostasis. Insulin release from pancreatic β-cells is mainly regulated by intracellular ATP-generating metabolic pathways. Hyperinsulinaemic hypoglycaemia (HH), the most common cause of severe and persistent hypoglycaemia in neonates and children, is the inappropriate secretion of insulin which occurs despite low plasma glucose levels leading to severe and persistent hypoketotic hypoglycaemia...
2017: International Journal of Pediatric Endocrinology
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
#9
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/28783164/effect-of-sequence-variants-on-variance-in-glucose-levels-predicts-type-2-diabetes-risk-and-accounts-for-heritability
#10
Erna V Ivarsdottir, Valgerdur Steinthorsdottir, Maryam S Daneshpour, Gudmar Thorleifsson, Patrick Sulem, Hilma Holm, Snaevar Sigurdsson, Astradur B Hreidarsson, Gunnar Sigurdsson, Ragnar Bjarnason, Arni V Thorsson, Rafn Benediktsson, Gudmundur Eyjolfsson, Olof Sigurdardottir, Isleifur Olafsson, Sirous Zeinali, Fereidoun Azizi, Unnur Thorsteinsdottir, Daniel F Gudbjartsson, Kari Stefansson
Sequence variants that affect mean fasting glucose levels do not necessarily affect risk for type 2 diabetes (T2D). We assessed the effects of 36 reported glucose-associated sequence variants on between- and within-subject variance in fasting glucose levels in 69,142 Icelanders. The variant in TCF7L2 that increases fasting glucose levels increases between-subject variance (5.7% per allele, P = 4.2 × 10(-10)), whereas variants in GCK and G6PC2 that increase fasting glucose levels decrease between-subject variance (7...
September 2017: Nature Genetics
https://www.readbyqxmd.com/read/28727166/hepatocytes-contribute-to-residual-glucose-production-in-a-mouse-model-for-glycogen-storage-disease-type-ia
#11
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
#12
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/28688303/effect-of-styrene-exposure-on-plasma-parameters-molecular-mechanisms-and-gene-expression-in-rat-model-islet-cells
#13
Kamal Niaz, Fatima Ismail Hassan, Faheem Mabqool, Fazlullah Khan, Saeideh Momtaz, Maryam Baeeri, Mona Navaei-Nigjeh, Mahban Rahimifard, Mohammad Abdollahi
Styrene is an aromatic hydrocarbon compound present in the environment and have primary exposure through plastic industry. The current study was designed to evaluate styrene-induced toxicity parameters in rat plasma fasting blood glucose (FBG) level, oral glucose tolerance, insulin secretion, oxidative stress, and inflammatory cytokines in cellular and molecular levels. Styrene was dissolved in corn oil and administered at different doses (250, 500, 1000, 1500, 2000mg/kg/day and control) to each rat, for 42days...
June 23, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28678435/molecular-mechanisms-of-action-of-styrene-toxicity-in-blood-plasma-and-liver
#14
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
#15
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/28597946/comprehensive-screening-for-monogenic-diabetes-in-89-japanese-children-with-insulin-requiring-antibody-negative-type-1-diabetes
#16
Kikumi Ushijima, Maki Fukami, Tadayuki Ayabe, Satoshi Narumi, Misako Okuno, Akie Nakamura, Toshikazu Takahashi, Kenji Ihara, Kazuhiro Ohkubo, Emiko Tachikawa, Shoji Nakayama, Junichi Arai, Nobuyuki Kikuchi, Toru Kikuchi, Tomoyuki Kawamura, Tatsuhiko Urakami, Kenichiro Hata, Kazuhiko Nakabayashi, Yoichi Matsubara, Shin Amemiya, Tsutomu Ogata, Ichiro Yokota, Shigetaka Sugihara
BACKGROUND: Mutations in causative genes for neonatal diabetes or maturity-onset diabetes of the young have been identified in multiple patients with autoantibody-negative type 1 diabetes (T1D). OBJECTIVES: We aimed to clarify the prevalence and phenotypic characteristics of monogenic abnormalities among 89 children with autoantibody-negative insulin-requiring T1D. METHODS: Mutations in 30 genes were screened using next-generation sequencing, and copy-number alterations of 4 major causative genes were examined using multiplex-ligation-dependent probe amplification...
June 9, 2017: Pediatric Diabetes
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
#17
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/28580277/expression-and-functional-assessment-of-candidate-type-2-diabetes-susceptibility-genes-identify-four-new-genes-contributing-to-human-insulin-secretion
#18
Fatou K Ndiaye, Ana Ortalli, Mickaël Canouil, Marlène Huyvaert, Clara Salazar-Cardozo, Cécile Lecoeur, Marie Verbanck, Valérie Pawlowski, Raphaël Boutry, Emmanuelle Durand, Iandry Rabearivelo, Olivier Sand, Lorella Marselli, Julie Kerr-Conte, Vikash Chandra, Raphaël Scharfmann, Odile Poulain-Godefroy, Piero Marchetti, François Pattou, Amar Abderrahmani, Philippe Froguel, Amélie Bonnefond
OBJECTIVES: Genome-wide association studies (GWAS) have identified >100 loci independently contributing to type 2 diabetes (T2D) risk. However, translational implications for precision medicine and for the development of novel treatments have been disappointing, due to poor knowledge of how these loci impact T2D pathophysiology. Here, we aimed to measure the expression of genes located nearby T2D associated signals and to assess their effect on insulin secretion from pancreatic beta cells...
June 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28575730/novel-glucokinase-gene-mutation-in-the-first-macedonian-family-tested-for-mody
#19
M Kocova, L Elblova, S Pruhova, J Lebl, P Dusatkova
We present a boy with mild hyperglycemia detected during an upper respiratory infection. Novel splicing mutation in the intron 1 of the GCK gene (c.45+1G>A) was detected, and was subsequently confirmed in his father. This is the first case of genetically confirmed Macedonian family with MODY.
May 10, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28555465/identification-of-maturity-onset-diabetes-of-the-young-caused-by-glucokinase-mutations-detected-using-whole-exome-sequencing
#20
Eun Hee Cho, Jae Woong Min, Sun Shim Choi, Hoon Sung Choi, Sang Wook Kim
Glucokinase maturity-onset diabetes of the young (GCK-MODY) represents a distinct subgroup of MODY that does not require hyperglycemia-lowering treatment and has very few diabetes-related complications. Three patients from two families who presented with clinical signs of GCK-MODY were evaluated. Whole-exome sequencing was performed and the effects of the identified mutations were assessed using bioinformatics tools, such as PolyPhen-2, SIFT, and in silico modeling. We identified two mutations: p.Leu30Pro and p...
June 2017: Endocrinology and Metabolism
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