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Diabetes methylation

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https://www.readbyqxmd.com/read/29026446/dna-methylation-links-genetics-fetal-environment-and-an-unhealthy-lifestyle-to-the-development-of-type-2-diabetes
#1
REVIEW
Emma Nilsson, Charlotte Ling
Type 2 diabetes is a complex trait with both environmental and hereditary factors contributing to the overall pathogenesis. One link between genes, environment, and disease is epigenetics influencing gene transcription and, consequently, organ function. Genome-wide studies have shown altered DNA methylation in tissues important for glucose homeostasis including pancreas, liver, skeletal muscle, and adipose tissue from subjects with type 2 diabetes compared with nondiabetic controls. Factors predisposing for type 2 diabetes including an adverse intrauterine environment, increasing age, overweight, physical inactivity, a family history of the disease, and an unhealthy diet have all shown to affect the DNA methylation pattern in target tissues for insulin resistance in humans...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/29020168/association-of-dna-methylation-based-biological-age-with-health-risk-factors-and-overall-and-cause-specific-mortality
#2
Pierre-Antoine Dugué, Julie K Bassett, JiHoon E Joo, Laura Baglietto, Chol-Hee Jung, Ee Ming Wong, Giovanni Fiorito, Daniel Schmidt, Enes Makalic, Shuai Li, Margarita Moreno-Betancur, Daniel D Buchanan, Paolo Vineis, Dallas R English, John L Hopper, Gianluca Severi, Melissa C Southey, Graham G Giles, Roger L Milne
Measures of biological age based on blood DNA methylation, referred to as age acceleration (AA), have been developed. We examined whether AA was associated with health risk factors and overall and cause-specific mortality. At baseline (1990-1994), blood samples were drawn from 2818 participants in the Melbourne Collaborative Cohort Study. DNA methylation was determined using the Illumina HM450K array. Mixed-effects models were used to examine the association of AA with health risk factors. Cox models were used to assess the association of AA with mortality...
August 17, 2017: American Journal of Epidemiology
https://www.readbyqxmd.com/read/28994286/a-novel-derivative-of-bardoxolone-methyl-improves-safety-for-treatment-of-diabetic-nephropathy
#3
Zhangjian Huang, Yi Mou, Xiaojun Xu, Di Zhao, Yisheng Lai, Yuwen Xu, Cen Chen, Ping Li, Sixun Peng, Jide Tian, Yihua Zhang
Currently, no effective and safe medicines are available to treat diabetic nephropathy (DN). Bardoxolone methyl (CDDO-Me) has displayed promising anti-DN activity but serious side-effects in the clinical trial, probably because the highly reactive α-cyano-α,β-unsaturated ketone (CUK) in ring A of CDDO-Me can covalently bind to thiol functionalities in many biomacromolecules. In this study, we designed and synthesized a γ-glutamyl transpeptidase (GGT)-based and CUK-modified derivative 2 of CDDO-Me to address this issue...
October 10, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28993426/effect-of-diabetes-status-and-hyperglycemia-on-global-dna-methylation-and-hydroxymethylation
#4
Jairo Arturo Pinzón-Cortés, Angelina Perna-Chaux, Nicolás Steven Rojas-Villamizar, Angelica Diaz-Basabe, Diana Carolina Polania-Villanueva, María Fernanda Jacome, Carlos Olimpo Mendivil, Helena Groot, Valeriano López-Segura
Type 2 diabetes mellitus (T2DM) is characterized by oxidative stress that could lead to chronic micro- and macro-vascular complications. We hypothesized that some of the target organ damage is mediated by oxidative alterations in epigenetic mechanisms involving DNA methylation (5mC) and DNA hydroxymethylation (5hmC). We analyzed global DNA methylation and hydroxymethylation in peripheral blood cells in well-controlled and poorly controlled patients with type 2 diabetes mellitus and compared them to healthy controls...
October 9, 2017: Endocrine Connections
https://www.readbyqxmd.com/read/28979999/therapeutic-effects-of-a-novel-agonist-of-peroxisome-proliferator-activated-receptor-alpha-for-the-treatment-of-diabetic-retinopathy
#5
Guotao Deng, Elizabeth P Moran, Rui Cheng, Greg Matlock, Kelu Zhou, David Moran, Danyang Chen, Qiang Yu, Jian-Xing Ma
Purpose: Clinical studies have shown that peroxisome proliferator-activated receptor alpha (PPARα) agonist fenofibrate has therapeutic effects on diabetic retinopathy (DR). The purpose of this study was to identify a novel PPARα agonist and to evaluate its beneficial effects on DR. Methods: The transcriptional activity of PPARα was measured by a luciferase-based promoter assay. TUNEL was used to evaluate apoptosis in retinal precursor cells (R28). Diabetes was induced in rats by injection of streptozotocin...
October 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28969637/the-role-of-endothelial-nitric-oxide-in-the-anti-restenotic-effects-of-liraglutide-in-a-mouse-model-of-restenosis
#6
Hideki Kushima, Yusaku Mori, Masakazu Koshibu, Munenori Hiromura, Kyoko Kohashi, Michishige Terasaki, Tomoyasu Fukui, Tsutomu Hirano
BACKGROUND: Previous animal studies have shown that glucagon-like peptide-1 receptor agonists (GLP-1RAs) suppress arterial restenosis, a major complication of angioplasty, presumably through their direct action on vascular smooth muscle cells. However, the contribution of vascular endothelial cells (VECs) to this process remains unknown. In addition, the potential interference caused by severe hyperglycemia and optimal treatment regimen remain to be determined. METHODS: Nine-week-old male C57BL6 (wild-type) and diabetic db/db mice were randomly divided into vehicle or liraglutide treatment groups (Day 1), and subject to femoral artery wire injuries (Day 3)...
October 2, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28967791/adipose-tissue-dna-methylome-changes-in-development-of-new-onset-diabetes-after-kidney-transplantation
#7
Saurabh Baheti, Prachi Singh, Yun Zhang, Jared Evans, Michael D Jensen, Virend K Somers, Jean-Pierre A Kocher, Zhifu Sun, Harini A Chakkera
AIM: New-onset diabetes after kidney transplant (NODAT) adversely impacts kidney allograft and patient survival. Epigenetic alterations in adipose tissue like DNA methylation may play a contributory role. METHODS: Adipose tissue DNA of the patients with NODAT and their age, sex and BMI matched controls (nine each) were sequenced by reduced representation bisulfite sequencing. Differentially methylated CpGs (DMCs) and differentially methylated regions (DMRs) were studied...
October 2, 2017: Epigenomics
https://www.readbyqxmd.com/read/28963949/dacryodes-edulis-enhances-antioxidant-activities-suppresses-dna-fragmentation-in-oxidative-pancreatic-and-hepatic-injuries-and-inhibits-carbohydrate-digestive-enzymes-linked-to-type-2-diabetes
#8
Ochuko L Erukainure, Ramgopal Mopuri, Olajumoke A Oyebode, Neil A Koorbanally, Md Shahidul Islam
The leaves of Dacryodes edulis were investigated for their anti-oxidative and anti-diabetic potentials in vitro. Extracts from sequential extraction with solvents of increasing polarity (n-hexane, ethyl acetate, ethanol and aqueous) of the leaves were subjected to in vitro antioxidant assays using the 2,2'-diphenyl-1-picrylhydrazyl (DPPH) scavenging and Ferric reducing antioxidant power (FRAP) protocols respectively. Their inhibitory effects were investigated on α-glucosidase, pancreatic lipases, pancreatic ATPase and glucose-6-phospatase activities...
September 27, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28958695/high-intake-of-dietary-advanced-glycation-end-products-is-associated-with-increased-arterial-stiffness-and-inflammation-in-subjects-with-type-2-diabetes
#9
A Di Pino, W Currenti, F Urbano, R Scicali, S Piro, F Purrello, A M Rabuazzo
BACKGROUND AND AIMS: Modern diets are high in advanced glycation end-products (dAGEs), derived from processing methods, exerting a pivotal role in promoting atherosclerotic risk. In this cross-sectional study we investigate the relationship between dAGE intake, arterial stiffness, inflammatory profile and macronutrient composition, in subjects with type 2 diabetes without overt cardiovascular disease. METHODS AND RESULTS: Arterial stiffness, carboxy-methyl-lysine, endogenous secretory receptor for AGEs (esRAGE), high sensitivity C reactive protein (hs-CRP), S100A12 and macronutrient intake were evaluated in 85 subjects with type 2 diabetes...
July 8, 2017: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/28957425/a-tissue-specific-promoter-derived-from-a-sine-retrotransposon-drives-biallelic-expression-of-plagl1-in-human-lymphocytes
#10
Claire E L Smith, Alexia Alexandraki, Sarah F Cordery, Rekha Parmar, David T Bonthron, Elizabeth M A Valleley
The imprinted gene PLAGL1 is an important regulator of apoptosis and cell cycle arrest. Loss of its expression has been implicated in tumorigenesis in a range of different cancers, and overexpression during fetal development causes transient neonatal diabetes mellitus (TNDM). PLAGL1 lies within an imprinted region of chromosome 6q24, and monoallelic expression from the major, differentially methylated promoter (P1) occurs in most human tissues. However, in peripheral blood leukocytes, the active promoter (P2) is non-imprinted and drives biallelic transcription...
2017: PloS One
https://www.readbyqxmd.com/read/28956099/arsenite-and-methylarsonite-inhibit-mitochondrial-metabolism-and-glucose-stimulated-insulin-secretion-in-ins-1-832-13-%C3%AE-cells
#11
E N Dover, R Beck, M C Huang, C Douillet, Z Wang, E L Klett, Miroslav Stýblo
Growing evidence suggests that exposure to environmental contaminants contributes to the current diabetes epidemic. Inorganic arsenic (iAs), a drinking water and food contaminant, is one of the most widespread environmental diabetogens according to epidemiological studies. Several schemes have been proposed to explain the diabetogenic effects of iAs exposure; however, the exact mechanism remains unknown. We have shown that in vitro exposure to low concentrations of arsenite (iAs(III)) or its trivalent methylated metabolites, methylarsonite (MAs(III)) and dimethylarsinite (DMAs(III)), inhibits glucose-stimulated insulin secretion (GSIS) from isolated pancreatic islets, with little effect on insulin transcription or total insulin content...
September 27, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28952001/exposures-to-arsenite-and-methylarsonite-produce-insulin-resistance-and-impair-insulin-dependent-glycogen-metabolism-in-hepatocytes
#12
Chongben Zhang, Emily M J Fennel, Christelle Douillet, Miroslav Stýblo
Environmental exposure to inorganic arsenic (iAs) has been shown to disturb glucose homeostasis, leading to diabetes. Previous laboratory studies have suggested several mechanisms that may underlie the diabetogenic effects of iAs exposure, including (i) inhibition of insulin signaling (leading to insulin resistance) in glucose metabolizing peripheral tissues, (ii) inhibition of insulin secretion by pancreatic β cells, and (iii) dysregulation of the methylation or expression of genes involved in maintenance of glucose or insulin metabolism and function...
September 26, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28947923/an-epigenome-wide-association-study-in-whole-blood-of-measures-of-adiposity-among-ghanaians-the-rodam-study
#13
Karlijn A C Meeks, Peter Henneman, Andrea Venema, Tom Burr, Cecilia Galbete, Ina Danquah, Matthias B Schulze, Frank P Mockenhaupt, Ellis Owusu-Dabo, Charles N Rotimi, Juliet Addo, Liam Smeeth, Silver Bahendeka, Joachim Spranger, Marcel M A M Mannens, Mohammad H Zafarmand, Charles Agyemang, Adebowale Adeyemo
BACKGROUND: Epigenome-wide association studies (EWAS) have identified DNA methylation loci involved in adiposity. However, EWAS on adiposity in sub-Saharan Africans are lacking despite the high burden of adiposity among African populations. We undertook an EWAS for anthropometric indices of adiposity among Ghanaians aiming to identify DNA methylation loci that are significantly associated. METHODS: The Illumina 450k DNA methylation array was used to profile DNA methylation in whole blood samples of 547 Ghanaians from the Research on Obesity and Diabetes among African Migrants (RODAM) study...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28947922/diabetes-medication-associates-with-dna-methylation-of-metformin-transporter-genes-in-the-human-liver
#14
Sonia García-Calzón, Alexander Perfilyev, Ville Männistö, Vanessa D de Mello, Emma Nilsson, Jussi Pihlajamäki, Charlotte Ling
BACKGROUND: Given that metformin is the most common pharmacological therapy for type 2 diabetes, understanding the function of this drug is of great importance. Hepatic metformin transporters are responsible for the pharmacologic action of metformin. However, epigenetics in genes encoding metformin transporters has not been fully elucidated. We examined the DNA methylation of these genes in the liver of subjects with type 2 diabetes and tested whether epigenetic alterations associate with diabetes medication, i...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28938426/a-sustained-activation-of-pancreatic-nmdars-is-a-novel-factor-of-%C3%AE-cell-apoptosis-and-dysfunction
#15
Xiao-Ting Huang, Shao-Jie Yue, Chen Li, Yan-Hong Huang, Qing-Mei Cheng, Xiao-Hong Li, Cai-Xia Hao, Ling-Zhi Wang, Jian-Ping Xu, Ming Ji, Chen Chen, Dan-Dan Feng, Zi-Qiang Luo
Type 2 diabetes, which features β-cell failure, is caused by the decrease of β-cell mass and insulin secretory function. Current treatments fail to halt the decrease of functional β-cell mass. Strategies to prevent β-cell apoptosis and dysfunction are highly desirable. Recently, our group and others have reported that blockade of N-methyl-D-aspartate receptors (NMDARs) in the islets has been proposed to prevent the progress of type 2 diabetes through improving β-cell function. It suggests that a sustained activation of the NMDARs may exhibit deleterious effect on β-cells...
September 4, 2017: Endocrinology
https://www.readbyqxmd.com/read/28935419/red-near-infrared-light-stimulates-release-of-an-endothelium-dependent-vasodilator-and-rescues-vascular-dysfunction-in-a-diabetes-model
#16
Agnes Keszler, Brian Lindemer, Dorothee Weihrauch, Deron Jones, Neil Hogg, Nicole L Lohr
Peripheral artery disease (PAD) is a morbid condition whereby ischemic peripheral muscle causes pain and tissue breakdown. Interestingly, PAD risk factors, e.g. diabetes mellitus, cause endothelial dysfunction secondary to decreased nitric oxide (NO) levels, which could explain treatment failures. Previously, we demonstrated 670nm light (R/NIR) increased NO from nitrosyl-heme stores, therefore we hypothesized R/NIR can stimulate vasodilation in healthy and diabetic blood vessels. Vasodilation was tested by ex vivo pressure myography in wild type C57Bl/6, endothelial nitric oxide synthase (eNOS) knockout, and db/db mice (10mW/cm(2) for 5min with 10min dark period)...
September 19, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28933769/a-lanosteryl-triterpene-from-protorhus-longifolia-improves-glucose-tolerance-and-pancreatic-beta-cell-ultrastructure-in-type-2-diabetic-rats
#17
Sihle E Mabhida, Rebamang A Mosa, Dambudzo Penduka, Foluso O Osunsanmi, Phiwayinkosi V Dludla, Tryana G Djarova, Andy R Opoku
Type 2 diabetes remains one of the leading causes of death worldwide. Persistent hyperglycemia within a diabetic state is implicated in the generation of oxidative stress and aggravated inflammation that is responsible for accelerated modification of pancreatic beta cell structure. Here we investigated whether a lanosteryl triterpene, methyl-3β-hydroxylanosta-9,24-dien-21-oate (RA-3), isolated from Protorhus longifolia can improve glucose tolerance and pancreatic beta cell ultrastructure by reducing oxidative stress and inflammation in high fat diet and streptozotocin-induced type 2 diabetes in rats...
July 26, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28933311/mg17-a-novel-triazole-derivative-abrogated-neuroinflammation-and-related-neurodegenerative-symptoms-in-rodents
#18
Gangadhar Matharasala, Ganesh Samala, Yogeeswari Perumal
The objective of present study is to explore multiple effects of the compound MG17 and relate them to achieve better therapeutic potential against neuroinflammation related disorders. We examined whether our compound is acting through regulating neuroinflammatory mediators. We have done some preliminary behavioral studies to shortlist the derivatives using rodent models of peripheral nerve injury in our earlier publication and now we extended our screening studies to explore the test compounds efficacy on other related peripheral neurological disorders such as Streptozotocin-induced diabetic peripheral neuropathy (DPN) and methyl mercury (MeHg) induced neurodegeneration in rats...
September 19, 2017: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/28932450/a-new-solvate-of-epalerstat-a-drug-for-diabetic-neuropathy
#19
Okky Dwichandra Putra, Daiki Umeda, Kaori Fukuzawa, Mihoko Gunji, Etsuo Yonemochi
Epalerstat {systematic name: (5Z)-5-[(2E)-2-methyl-3-phenyl-prop-2-en-1-yl-idene]-4-oxo-2-sulfanyl-idene-1,3-thia-zolidine-3-acetic acid} crystallized as an acetone monosolvate, C15H13NO3S2·C3H6O. In the epalerstat mol-ecule, the methyl-propyl-enediene moiety is inclined to the phenyl ring and the five-membered rhodamine ring by 21.4 (4) and 4.7 (4)°, respectively. In addition, the acetic acid moiety is found to be almost normal to the rhodamine ring, making a dihedral angle of 85.1 (2)°. In the crystal, a pair of O-H⋯O hydrogen bonds between the carb-oxy-lic acid groups of epalerstat mol-ecules form inversion dimers with an R2(2)(8) loop...
July 1, 2017: Acta Crystallographica. Section E, Crystallographic Communications
https://www.readbyqxmd.com/read/28927592/preliminary-structural-characterization-and-hypoglycemic-effects-of-an-acidic-polysaccharide-serp1-from-the-residue-of-sarcandra-glabra
#20
Wei Liu, Weisheng Lu, Yin Chai, Yameng Liu, Wenbing Yao, Xiangdong Gao
An acidic polysaccharide (SERP1) was isolated from the residue of Sarcandra glabra (Thunb.) Nakai by water extraction and purified by decoloration and ion exchange chromatography. The structure of SERP1 was determined by HPLC, HPSEC-MALLS, FT-IR, and NMR. The results indicated that SERP1 was a homogeneous heteropolysaccharide with the absolute molecular weight of 4.208×10(4)Da in the aqueous phase. 1,4-linked α-d-galacturonic acid, methyl esterified 1,4-linked α-d-galacturonic acid, 1,4-linked α-d-glucuronic acid, 1,5-linked α-l-arabinose, 1,3-linked β-d-galactose 1,4-linked α-d-glucose, 1,4,6-linked β-d-glucose, 1,6-linked β-d-glucose, and 1,2-linked rhamnose existed in SERP1...
November 15, 2017: Carbohydrate Polymers
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