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Glucokinase

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https://www.readbyqxmd.com/read/28094769/ipsc-derived-%C3%AE-cells-model-diabetes-due-to-glucokinase-deficiency
#1
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
#2
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
#3
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 This study aims to establish a national registry of MODY cases in Brazilian patients, assessing published and unpublished data. METHODS: 311 patients with clinical characteristics of MODY were analyzed, with unpublished data on 298 individuals described in 12 previous publications and 13 newly described cases in this report...
October 22, 2016: 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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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...
January 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/27882918/hyperglycaemia-induces-metabolic-dysfunction-and-glycogen-accumulation-in-pancreatic-%C3%AE-cells
#12
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
#13
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
#14
Joost Groot, Sidney C Cepress-Mclean, Adam Robbins-Pianka, Rob Knight, Ryan T Gill
Engineering the simultaneous consumption of glucose and xylose sugars is critical to enable the sustainable production of biofuels from lignocellulosic 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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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 (12.5 μM). 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 23, 2016: Journal of Agricultural and Food Chemistry
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