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Glucokinase

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https://www.readbyqxmd.com/read/29784881/structural-basis-for-adp-dependent-glucokinase-inhibition-by-8-bromo-substituted-adenosine-nucleotide
#1
Przemyslaw Grudnik, Marcin M Kaminski, Krzysztof P Rembacz, Katarzyna Kuska, Mariusz Madej, Jan Potempa, Maciej Dawidowski, Grzegorz Dubin
In higher eukaryotes, several ATP-utilizing enzymes known as hexokinases activate glucose in the glycolysis pathway by phosphorylation to glucose-6-phosphate. In contrast to canonical hexokinases which use ATP, ADP-dependent glucokinase (ADPGK) catalyzes non-canonical phosphorylation of glucose to glucose-6-phosphate using ADP as a phosphate donor. Initially discovered in Archaea, the human homolog of ADPGK was described only recently. ADPGK's involvement in modified bioenergetics of activated T cells has been postulated and elevated ADPGK expression has been reported in various cancer tissues...
May 21, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29760458/hyperglycemia-does-not-affect-tissue-repair-responses-in-shear-stress-induced-atherosclerotic-plaques-in-apoe-mice
#2
Sabrina Hsiung, Anki Knutsson, Jenifer Vallejo, Pontus Dunér, Suvi E Heinonen, Ann-Cathrine Jönsson-Rylander, Eva Bengtsson, Jan Nilsson, Anna Hultgårdh-Nilsson
The mechanisms responsible for macrovascular complications in diabetes remain to be fully understood. Recent studies have identified impaired vascular repair as a possible cause of plaque vulnerability in diabetes. This notion is supported by observations of a reduced content of fibrous proteins and smooth muscle cell mitogens in carotid endarterectomy from diabetic patients along with findings of decreased circulating levels of endothelial progenitor cells. In the present study we used a diabetic mouse model to characterize how hyperglycemia affects arterial repair responses...
May 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29753302/contribution-of-hepatic-retinaldehyde-dehydrogenase-induction-to-impairment-of-glucose-metabolism-by-high-fat-diet-feeding-in-c57bl-6j-mice
#3
Jiong Xu, Mian Zhang, Xiangping Zhang, Hanyu Yang, Binbin Sun, Zhongjian Wang, Yaqian Zhou, Shuting Wang, Xiaodong Liu, Li Liu
Obesity and insulin resistance are associated with overexpression of retinaldehyde dehydrogenase 1 (RALDH1). We aimed to investigate the roles of hepatic RALDH1 induction in glucose metabolism impairment using mice fed with high-fat diet (HFD). Mice were fed with HFD for 8 weeks and treated with RALDH inhibitor citral for another 4 weeks. Oral glucose tolerance test (OGTT), pyruvate tolerance test (PTT) and insulin tolerance test (ITT) were operated. Expressions of Phosphoenolpyruvate carboxykinase 1 (PCK1), glucokinase (GCK) and RALDH1 were measured...
May 12, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29752268/preferred-hexoses-influence-long-term-memory-and-induction-of-lactose-catabolism-by-streptococcus-mutans
#4
Lin Zeng, Lulu Chen, Robert A Burne
Bacteria prioritize sugar metabolism via carbohydrate catabolite repression, which regulates global gene expression to optimize the catabolism of preferred substrates. Here, we report an unusual long-term memory effect in certain Streptococcus mutans strains that alters adaptation to growth on lactose after prior exposure to glucose or fructose. In strain GS-5, cells that were first cultured on fructose then transferred to lactose displayed an exceptionally long lag (>11 h) and slower growth, compared to cells first cultured on glucose or cellobiose, which displayed a reduction in lag phase by as much as 10 h...
May 11, 2018: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29749571/hepatic-irs1-and-%C3%A3-catenin-expression-is-associated-with-histological-progression-and-overt-diabetes-emergence-in-nafld-patients
#5
Kenichiro Enooku, Mayuko Kondo, Naoto Fujiwara, Takayoshi Sasako, Junji Shibahara, Akira Kado, Kazuya Okushin, Hidetaka Fujinaga, Takeya Tsutsumi, Ryo Nakagomi, Tatsuya Minami, Masaya Sato, Hayato Nakagawa, Yuji Kondo, Yoshinari Asaoka, Ryosuke Tateishi, Kohjiro Ueki, Hitoshi Ikeda, Haruhiko Yoshida, Kyoji Moriya, Hiroshi Yotsuyanagi, Takashi Kadowaki, Masashi Fukayama, Kazuhiko Koike
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a risk factor for type 2 diabetes. Our aim was to investigate the relationship between NAFLD and impaired glucose metabolism in terms of insulin receptor substrate 1 and 2 (IRS1 and IRS2) expression in the liver. METHODS: Liver biopsy was performed at the University of Tokyo Hospital between November 2011 and March 2016 on 146 patients with NAFLD who were not being treated with any diabetes or dyslipidemia drugs...
May 10, 2018: Journal of Gastroenterology
https://www.readbyqxmd.com/read/29748994/hypothalamic-arcuate-nucleus-glucokinase-regulates-insulin-secretion-and-glucose-homeostasis
#6
Yue Ma, Risheka Ratnasabapathy, Chioma Izzi-Engbeaya, Marie-Sophie Nguyen-Tu, Errol Richardson, Sufyan Hussain, Ivan De Backer, Christopher Holton, Mariana Norton, Gaelle Carrat, Blanche Schwappach, Guy A Rutter, Waljit S Dhillo, James Gardiner
AIMS: Glucokinase (GK) serves as a glucose sensor in several tissues including glucose-sensitive neurons of the arcuate nucleus within the hypothalamus. We have previously demonstrated a role for arcuate GK in the regulation of food and glucose intake. However, its role in the regulation of glucose homeostasis is less clear. We therefore sought to investigate the role of arcuate GK in the regulation of glucose homeostasis. MATERIALS AND METHODS: Recombinant adeno-associated virus expressing either GK or an antisense GK construct was used to alter GK activity specifically in the hypothalamic arcuate nucleus...
May 11, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29744293/comparative-metabolomics-and-glycolysis-enzyme-profiling-of-embryogenic-and-nonembryogenic-grape-cells
#7
Jonathan Parrilla, Cécile Gaillard, Jérémy Verbeke, Mickaël Maucourt, Radoslav A Aleksandrov, Florence Thibault, Pierrette Fleurat-Lessard, Yves Gibon, Dominique Rolin, Rossitza Atanassova
A novel biological model was created for the comparison of grapevine embryogenic cells (EC) and nonembryogenic cells (NEC) sharing a common genetic background but distinct phenotypes, when cultured on their respective most appropriate media. Cytological characterization, 1 H-NMR analysis of intracellular metabolites, and glycolytic enzyme activities provided evidence for the marked metabolic differences between EC and NEC. The EC were characterized by a moderate and organized cell proliferation, coupled with a low flux through glycolysis, high capacity of phosphoenolpyruvate carboxylase and glucokinase, and high oxygen consumption...
May 2018: FEBS Open Bio
https://www.readbyqxmd.com/read/29735394/dorzagliatin-monotherapy-in-chinese-patients-with-type-2-diabetes-a-dose-ranging-randomised-double-blind-placebo-controlled-phase-2-study
#8
Dalong Zhu, Shenglian Gan, Yu Liu, Jianhua Ma, Xiaolin Dong, Weihong Song, Jiao'e Zeng, Guixia Wang, Wenjuan Zhao, Qiu Zhang, Yukun Li, Hui Fang, Xiaofeng Lv, Yongquan Shi, Haoming Tian, Linong Ji, Xin Gao, Lihui Zhang, Yuqian Bao, Minxiang Lei, Ling Li, Longyi Zeng, Xiaoying Li, Xinghua Hou, Yu Zhao, Tianxin Hu, Xiaoyun Ge, Guiyu Zhao, Yongguo Li, Yi Zhang, Li Chen
BACKGROUND: Glucokinase acts as a glucose sensor in the pancreas and a glucose processor in the liver, and has a central role in glucose homoeostasis. Dorzagliatin is a new, dual-acting, allosteric glucokinase activator that targets both pancreatic and hepatic glucokinases. Dorzagliatin has good pharmacokinetic and pharmacodynamic properties in humans, and provides effective 24-h glycaemic control and improves glucose sensitivity in patients with type 2 diabetes. We aimed to assess the efficacy and safety of dorzagliatin monotherapy at different doses in Chinese patients with type 2 diabetes...
May 4, 2018: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/29735393/new-hope-for-glucokinase-activators-in-type-2-diabetes
#9
André J Scheen
No abstract text is available yet for this article.
May 4, 2018: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/29717618/glucocorticoid-signaling-enhances-expression-of-glucose-sensing-molecules-in-immature-pancreatic-beta-like-cells-derived-from-murine-embryonic-stem-cells-in-vitro
#10
Nadiah Ghazalli, Xiaoxing Wu, Stephanie Walker, Nancy Trieu, Li-Yu Hsin, Justin Choe, Chialin Chen, Jasper Hsu, Jeanne LeBon, Mark T Kozlowski, Jeffrey Rawson, David A Tirrell, M L Richard Yip, Hsun Teresa Ku
Pluripotent stem cells may serve as an alternative source of beta-like cells for replacement therapy of type 1 diabetes; however, the beta-like cells generated in many differentiation protocols are immature. The maturation of endogenous beta cells involves an increase in insulin expression starting in late gestation and a gradual acquisition of the abilities to sense glucose and secrete insulin by week 2 after birth in mice; however, what molecules regulate these maturation processes are incompletely known...
May 2, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29716943/hepatic-glucose-metabolic-responses-to-digestible-dietary-carbohydrates-in-two-isogenic-lines-of-rainbow-trout
#11
X Song, L Marandel, M Dupont-Nivet, E Quillet, I Geurden, S Panserat
Rainbow trout ( Oncorhynchus mykiss ) was recognized as typical "glucose-intolerant" fish and poor dietary carbohydrate user. Our first objective was to test the effect of dietary carbohydrates itself (without modification of dietary protein intake) on hepatic glucose gene expression (taking into account of the paralogs. The second aim was to research if two isogenic trout lines had different responds to carbohydrate intake, showing one with a better use dietary carbohydrates. Thus, we used two isogenic lines of rainbow trout (named A32h and AB1h) fed with either high carbohydrate diet or low carbohydrate diet for 12 weeks...
May 1, 2018: Biology Open
https://www.readbyqxmd.com/read/29707866/dorzagliatin-hms5552-a-novel-dual-acting-glucokinase-activator-improves-glycemic-control-and-pancreatic-%C3%AE-cell-function-in-patients-with-type-2-diabetes-a-28-day-treatment-study-using-biomarker-guided-patient-selection
#12
Xiao-Xue Zhu, Da-Long Zhu, Xiao-Ying Li, Ya-Lin Li, Xiao-Wei Jin, Tian-Xin Hu, Yu Zhao, Yong-Guo Li, Gui-Yu Zhao, Shuang Ren, Yi Zhang, Yan-Hua Ding, Li Chen
AIMS: To investigate pharmacokinetics and pharmacodynamics of a dual acting glucokinase activator dorzagliatin and its safety, tolerability and effect on pancreatic β-cell function in Chinese type 2 diabetes patients. MATERIALS AND METHODS: Twenty-four T2D subjects were selected utilizing a set of predefined clinical biomarkers. They were randomized to receive dorzagliatin 75mg twice or once a day (BID, QD) for 28 days. Changes in HbA1c and glycemic parameters from baseline to Day 28 were assessed...
April 29, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29704611/functional-characterization-of-mody2-mutations-in-the-nuclear-export-signal-of-glucokinase
#13
Angel Gutierrez-Nogués, Carmen-María García-Herrero, Josep Oriola, Olivier Vincent, María-Angeles Navas
Glucokinase (GCK) plays a key role in glucose homeostasis. Heterozygous inactivating mutations in the GCK gene cause the familial, mild fasting hyperglycaemia named MODY2. Besides its particular kinetic characteristics, glucokinase is regulated by subcellular compartmentation in hepatocytes. Glucokinase regulatory protein (GKRP) binds to GCK, leading to enzyme inhibition and import into the nucleus at fasting. When glucose concentration increases, GCK-GKRP dissociates and GCK is exported to the cytosol due to a nuclear export signal (NES)...
July 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29684600/effect-of-high-dietary-starch-levels-on-growth-hepatic-glucose-metabolism-oxidative-status-and-immune-response-of-juvenile-largemouth-bass-micropterus-salmoides
#14
Shi-Mei Lin, Chao-Ming Shi, Ming-Ming Mu, Yong-Jun Chen, Li Luo
An experimental trial was conducted to investigate the effects of high dietary starch levels on growth, hepatic glucose metabolism enzyme, antioxidant capacity and immune responses of largemouth bass, Micropterus salmoides. Fish (initial body weight: 16.9 ± 0.24 g) were fed three isonitrogenous and isoenergetic semi-purified diets containing 5%, 10% and 20% wheat starch, respectively. The results indicated that fish fed 5% and 10% starch diets showed significantly better weight gain, specific growth rate (SGR), protein efficiency ratio (PER) and feed conversion ratio (FCR) compared with that fed 20% starch diet...
April 20, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29679800/synthetic-investigation-of-binary-ternary-cr-iii-hydroxycarboxylic-acid-aromatic-chelator-systems-structure-specific-influence-on-adipogenic-biomarkers-linked-to-insulin-mimesis
#15
O Tsave, C Gabriel, M Kafantari, M Yavropoulou, J G Yovos, C P Raptopoulou, V Psycharis, A Terzis, C Mateescu, A Salifoglou
In an attempt to understand the aqueous interactions of Cr(III) with low-molecular mass physiological ligands and examine its role as an adipogenic metallodrug agent in Diabetes mellitus II, the pH-specific synthesis in the binary-ternary Cr(III)-(HA = hydroxycarboxylic acid)-(N,N)-aromatic chelator (AC) (HA = 2-hydroxyethyl iminodiacetic acid/heidaH2 , quinic acid; AC = 1,10-phenanthroline/phen) systems was pursued, leading to four new crystalline compounds. All materials were characterized by elemental analysis, UV-Visible, FT-IR, and ESI-MS spectroscopy, cyclic voltammetry, and X-Ray crystallography...
February 10, 2018: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/29670171/author-correction-pyridoxine-dipharmacophore-derivatives-as-potent-glucokinase-activators-for-the-treatment-of-type-2-diabetes-mellitus
#16
Mikhail S Dzyurkevich, Denis A Babkov, Nikita V Shtyrlin, Olga Yu Mayka, Alfiya G Iksanova, Pavel M Vassiliev, Konstantin V Balakin, Alexander A Spasov, Vadim V Tarasov, George Barreto, Yurii G Shtyrlin, Gjumrakch Aliev
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
April 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29669254/regulatory-t-cell-migration-is-dependent-on-glucokinase-mediated-glycolysis
#17
Madhav Kishore, Kenneth C P Cheung, Hongmei Fu, Fabrizia Bonacina, Guosu Wang, David Coe, Eleanor J Ward, Alessandra Colamatteo, Maryam Jangani, Andrea Baragetti, Giuseppe Matarese, David M Smith, Robert Haas, Claudio Mauro, David C Wraith, Klaus Okkenhaug, Alberico L Catapano, Veronica De Rosa, Giuseppe D Norata, Federica M Marelli-Berg
No abstract text is available yet for this article.
April 17, 2018: Immunity
https://www.readbyqxmd.com/read/29667486/lncrna-adpgk-as1-promotes-pancreatic-cancer-progression-through-activating-zeb1-mediated-epithelial-mesenchymal-transition
#18
Suzhen Song, Weihua Yu, Sen Lin, Mingbao Zhang, Teng Wang, Shuang Guo, Hongbo Wang
OBJECTIVE: This study was conducted to investigate the effects of ADP dependent glucokinase antisense RNA 1 (ADPGK-AS1)/ miR-205-5p/ zinc finger E-box binding homeobox 1 (ZEB1) on PC cells. METHODS: Differentially expressed lncRNAs and miRNAs in pancreatic cancer (PC) were identified by microarray analysis. In silico ceRNA analysis was conducted to find out the interactions among lncRNAs, miRNAs and mRNAs. Quantitative real-time PCR (qRT-PCR) was utilized to examine the expression of miR-205-5p and lncRNA ADPGK-AS1 in PC and non-cancerous cells...
April 18, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29651202/a-narrative-review-of-potential-future-antidiabetic-drugs-should-we-expect-more
#19
REVIEW
Gaurav Chikara, Pramod Kumar Sharma, Pradeep Dwivedi, Jaykaran Charan, Sneha Ambwani, Surjit Singh
Prevalence of diabetes mellitus, a chronic metabolic disease characterized by hyperglycemia, is growing worldwide. The majority of the cases belong to type 2 diabetes mellitus (T2DM). Globally, India ranks second in terms of diabetes prevalence among adults. Currently available classes of therapeutic agents are used alone or in combinations but seldom achieve treatment targets. Diverse pathophysiology and the need of therapeutic agents with more favourable pharmacokinetic-pharmacodynamics profile make newer drug discoveries in the field of T2DM essential...
April 2018: Indian Journal of Clinical Biochemistry: IJCB
https://www.readbyqxmd.com/read/29648519/glutamate-dehydrogenase-role-in-regulating-metabolism-and-insulin-release-in-pancreatic-%C3%AE-cells
#20
David F Wilson, Abigail T J Cember, Franz M Matschinsky
Regulation of insulin release and glucose homeostasis by pancreatic β-cells is dependent on the metabolism of glucose by glucokinase (GK) and the influence of that activity on oxidative phosphorylation. Genetic alterations that result in hyperactivity of mitochondrial glutamate dehydrogenase (GDH-1) can cause hypoglycemia-hyperammonemia following high protein meals, but the role of GDH-1 remains poorly understood. GDH-1 activity is strongly inhibited by GTP, to near zero in the absence of ADP, and cooperatively activated (n=2...
April 12, 2018: Journal of Applied Physiology
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