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Diabetes methylation

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https://www.readbyqxmd.com/read/28324172/enzymes-involved-in-branched-chain-amino-acid-metabolism-in-humans
#1
REVIEW
María M Adeva-Andany, Laura López-Maside, Cristóbal Donapetry-García, Carlos Fernández-Fernández, Cristina Sixto-Leal
Branched-chain amino acids (leucine, isoleucine and valine) are structurally related to branched-chain fatty acids. Leucine is 2-amino-4-methyl-pentanoic acid, isoleucine is 2-amino-3-methyl-pentanoic acid, and valine is 2-amino-3-methyl-butanoic acid. Similar to fatty acid oxidation, leucine and isoleucine produce acetyl-coA. Additionally, leucine generates acetoacetate and isoleucine yields propionyl-coA. Valine oxidation produces propionyl-coA, which is converted into methylmalonyl-coA and succinyl-coA. Branched-chain aminotransferase catalyzes the first reaction in the catabolic pathway of branched-chain amino acids, a reversible transamination that converts branched-chain amino acids into branched-chain ketoacids...
March 21, 2017: Amino Acids
https://www.readbyqxmd.com/read/28318634/dna-methyltransferase-1-may-be-a-therapy-target-for-attenuating-diabetic-nephropathy-and-podocyte-injury
#2
Li Zhang, Qianmei Zhang, Shuangxin Liu, Yuanhan Chen, Ruizhao Li, Ting Lin, Chunping Yu, Hong Zhang, Zhongshun Huang, Xinchen Zhao, Xiaofan Tan, Zhuo Li, Zhiming Ye, Jianchao Ma, Bin Zhang, Wenjian Wang, Wei Shi, Xinling Liang
The contribution of DNA methylation to diabetic nephropathy, especially the effect on podocyte integrity, is not clarified. Here we found that albuminuria in a db/db mouse model was markedly attenuated after treatment with a DNA methylation inhibitor. This was accompanied by alleviation of glomerular hypertrophy, mesangial matrix expansion, and podocyte injury. The expression of DNA methyltransferase 1 (Dnmt1), nuclear factor Sp1, and nuclear factor kappa B (NFκB)-p65 markedly increased in podocytes in vivo and in vitro under the diabetic state...
March 15, 2017: Kidney International
https://www.readbyqxmd.com/read/28304288/changes-in-synaptic-plasticity-and-glutamate-receptors-in-type-2-diabetic-kk-ay-mice
#3
Huajing Yin, Weiping Wang, Wenwen Yu, Jiang Li, Nan Feng, Ling Wang, Xiaoliang Wang
In the present study, the progressive alteration of cognition and the mechanisms of reduction in long-term potentiation (LTP) in spontaneous obese KK-Ay type 2 diabetic mice were investigated. In the study, 3-, 5-, and 7-month-old KK-Ay mice were used. The results indicated that KK-Ay mice showed cognitive deficits in the Morris water maze test beginning at the age of 3 months. LTP was significantly impaired in KK-Ay mice during whole study period (3 to 7 months). The above deficits were reversible at an early stage (3 to 5 months old) by diet intervention...
March 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28302722/amyloid-%C3%AE-oligomers-transiently-inhibit-amp-activated-kinase-and-cause-metabolic-defects-in-hippocampal-neurons
#4
Gisele S Seixas da Silva, Helen M Melo, Mychael V Lourenco, Natalia de M Lyra E Silva, Marcelo B de Carvalho, Soniza Alves-Leon, Jorge M de Souza, William L Klein, Wagner S da-Silva, Sergio T Ferreira, Fernanda G De Felice
AMP-activated kinase (AMPK) is a key player in energy sensing and metabolic reprogramming under cellular energy restriction. Several studies have linked impaired AMPK function to peripheral metabolic diseases such as diabetes. However, the impact of neurological disorders, such as Alzheimer disease (AD), on AMPK function and downstream effects of altered AMPK activity on neuronal metabolism have been investigated only recently. Here, we report the impact of A β oligomers (AβOs), synaptotoxins that accumulate in AD brains, on neuronal AMPK activity...
March 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28290602/ajs1669-a-novel-small-molecule-muscle-glycogen-synthase-activator-improves-glucose-metabolism-and-reduces-body-fat-mass-in-mice
#5
Kazuhiro Nakano, Sen Takeshita, Noriko Kawasaki, Wataru Miyanaga, Yoriko Okamatsu, Mizuki Dohi, Tadakiyo Nakagawa
Impaired glycogen synthesis and turnover are common in insulin resistance and type 2 diabetes. As glycogen synthase (GS) is a key enzyme involved in the synthetic process, it presents a promising therapeutic target for the treatment of type 2 diabetes. In the present study, we identified a novel, potent and orally available GS activator AJS1669 {sodium 2-[[5-[[4-(4,5-difluoro-2-methylsulfanyl-phenyl)phenoxy] methyl]furan-2-carbonyl]-(2-furylmethyl)amino] acetate}. In vitro, we performed a glycogen synthase 1 (GYS1) activation assay for screening GS activators and identified that the activity of AJS1669 was further potentiated in the presence of glucose-6-phosphate (G6P)...
March 7, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28289478/cerebral-white-matter-hyperintensities-on-mri-and-acceleration-of-epigenetic-aging-the-atherosclerosis-risk-in-communities-study
#6
Abhay Raina, Xiaoping Zhao, Megan L Grove, Jan Bressler, Rebecca F Gottesman, Weihua Guan, James S Pankow, Eric Boerwinkle, Thomas H Mosley, Myriam Fornage
BACKGROUND: Cerebral white matter hyperintensities (WMH) on magnetic resonance imaging (MRI) are part of the spectrum of brain vascular injury accompanying aging and are associated with a substantial risk of stroke and dementia. We investigated the association of cerebral WMH burden on MRI with a DNA methylation-based biomarker of aging, termed DNA methylation age acceleration, which represents the deviation of the DNA methylation-predicted age from the chronologic age. RESULTS: In this cross-sectional observational study of 713 African-American participants of the Atherosclerosis Risk in Communities study, aged 51-73 years, estimates of predicted age were obtained based on two algorithms (Hannum et al...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28286899/epigenetics-of-kidney-disease
#7
REVIEW
Nicola Wanner, Wibke Bechtel-Walz
DNA methylation and histone modifications determine renal programming and the development and progression of renal disease. The identification of the way in which the renal cell epigenome is altered by environmental modifiers driving the onset and progression of renal diseases has extended our understanding of the pathophysiology of kidney disease progression. In this review, we focus on current knowledge concerning the implications of epigenetic modifications during renal disease from early development to chronic kidney disease progression including renal fibrosis, diabetic nephropathy and the translational potential of identifying new biomarkers and treatments for the prevention and therapy of chronic kidney disease and end-stage kidney disease...
March 13, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28286315/formulation-of-hydrophobic-peptides-for-skin-delivery-via-coated-microneedles
#8
Xin Zhao, Sion A Coulman, Stephanie J Hanna, F Susan Wong, Colin M Dayan, James C Birchall
Microneedles (MNs) have been investigated as a minimally-invasive delivery technology for a range of active pharmaceutical ingredients (APIs). Various formulations and methods for coating the surface of MNs with therapeutics have been proposed and exemplified, predominantly for hydrophilic drugs and particulates. The development of effective MN delivery formulations for hydrophobic drugs is more challenging with dosing restrictions and the use of organic solvents impacting on both the bioactivity and the kinetics of drug release...
March 9, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28283910/hyperglycemia-impedes-definitive-endoderm-differentiation-of-human-embryonic-stem-cells-by-modulating-histone-methylation-patterns
#9
A C H Chen, Y L Lee, S W Fong, C C Y Wong, E H Y Ng, W S B Yeung
Exposure to maternal diabetes during fetal growth is a risk factor for the development of type II diabetes (T2D) in later life. Discovery of the mechanisms involved in this association should provide valuable background for therapeutic treatments. Early embryogenesis involves epigenetic changes including histone modifications. The bivalent histone methylation marks H3K4me3 and H3K27me3 are important for regulating key developmental genes during early fetal pancreas specification. We hypothesized that maternal hyperglycemia disrupted early pancreas development through changes in histone bivalency...
March 10, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28282966/experimental-mitochondria-targeted-dna-methylation-identifies-gpc-methylation-not-cpg-methylation-as-potential-regulator-of-mitochondrial-gene-expression
#10
Monique G P van der Wijst, Amanda Y van Tilburg, Marcel H J Ruiters, Marianne G Rots
Like the nucleus, mitochondria contain their own DNA and recent reports provide accumulating evidence that also the mitochondrial DNA (mtDNA) is subjective to DNA methylation. This evidence includes the demonstration of mitochondria-localised DNA methyltransferases and demethylases, and the detection of mtDNA methylation as well as hydroxymethylation. Importantly, differential mtDNA methylation has been linked to aging and diseases, including cancer and diabetes. However, functionality of mtDNA methylation has not been demonstrated...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28279198/sox9-transcriptionally-regulates-wnt-signaling-in-intestinal-epithelial-stem-cells-in-hypomethylated-crypts-in-the-diabetic-state
#11
Can-Ze Huang, Ji-Hao Xu, Wa Zhong, Zhong-Sheng Xia, Si-Yi Wang, Di Cheng, Jie-Yao Li, Ting-Feng Wu, Qi-Kui Chen, Tao Yu
BACKGROUND: Distinctive structures called crypts harbor intestinal epithelial stem cells (IESCs) which generate progenitor and terminally differentiated cells in the intestinal epithelium. Mammalian IESCs and their daughter cells require the participation of DNA methylation and the transcription factor Sox9 for proliferation and differentiation. However, the association between Sox9 and DNA methylation in this process remains elusive. METHODS: The DNA methylation of small intestinal epithelial crypts in db/db mice was detected via combining methylated DNA immunoprecipitation with microarray hybridization...
March 9, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28277977/human-liver-epigenetic-alterations-in-non-alcoholic-steatohepatitis-are-related-to-insulin-action
#12
Vanessa D de Mello, Ashok Matte, Alexander Perfilyev, Ville Männistö, Tina Rönn, Emma Nilsson, Pirjo Käkelä, Charlotte Ling, Jussi Pihlajamäki
Both genetic and lifestyle factors contribute to the risk of non-alcoholic steatohepatitis (NASH). Additionally, epigenetic modifications may also play a key role in the pathogenesis of NASH. We therefore investigated liver DNA methylation, as a marker for epigenetic alterations, in individuals with simple steatosis and NASH, and further tested if these alterations were associated with clinical phenotypes. Liver biopsies obtained from 95 obese individuals (age: 49.5±7.7 years, BMI: 43±5.7 kg/m(2), type 2 diabetes [T2D]: 35) as a wedge biopsy during a Roux-en-Y gastric bypass operation were investigated...
February 23, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28276790/new-onset-diabetes-mellitus-induced-by-statins-current-evidence
#13
Steven G Chrysant
The hydroxyl-methyl-glutaryl-coenzyme-A (HMG-CoA) reductase inhibitors of statin action are very effective and safe drugs, and they are widely used for the treatment of hyperlipidemia and the prevention of primary and secondary cardiovascular diseases (CVDs). However, recent meta-analyses of previous studies done with statins have shown that these drugs could induce new onset diabetes mellitus (NODM), especially in subjects prone to diabetes: obese, females, older age, Asian descent, and those with pre-diabetes or the metabolic syndrome...
February 24, 2017: Postgraduate Medicine
https://www.readbyqxmd.com/read/28273874/early-life-nutritional-programming-of-type-2-diabetes-experimental-and-quasi-experimental-evidence
#14
REVIEW
Alexander M Vaiserman
Consistent evidence from both experimental and human studies suggest that inadequate nutrition in early life can contribute to risk of developing metabolic disorders including type 2 diabetes (T2D) in adult life. In human populations, most findings supporting a causative relationship between early-life malnutrition and subsequent risk of T2D were obtained from quasi-experimental studies ('natural experiments'). Prenatal and/or early postnatal exposures to famine were demonstrated to be associated with higher risk of T2D in many cohorts around the world...
March 5, 2017: Nutrients
https://www.readbyqxmd.com/read/28273212/role-of-micrornas-in-the-treatment-of-type-2-diabetes-mellitus-with-roux-en-y-gastric-bypass
#15
Z Zhu, J Yin, D C Li, Z Q Mao
The aim of this study was to investigate the effect of Roux-en-Y gastric bypass (RYGB) on the peripheral blood microRNAs (miRNAs) of patients with type 2 diabetes mellitus (T2DM). miRNAs are small 20- to 22-nucleotide (nt) noncoding RNAs. They constitute a novel class of gene regulators that negatively regulate gene expression at the post-transcriptional level. miRNAs play an important role in several biological processes. Twelve patients with T2DM who were scheduled to undergo laparoscopic RYGB surgery were separated into two groups, using a body mass index of 30 kg/m2 as a cut-off point...
March 2, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28270441/insulin-sensitizer-prevents-and-ameliorates-experimental-type-1-diabetes
#16
Michael Valitsky, Amnon Hoffman, Terry Unterman, Jacob Bar-Tana
Insulin-dependent type-1 diabetes (T1D) is driven by autoimmune beta-cell failure, whereas systemic resistance to insulin is considered the hallmark of insulin-independent type-2 diabetes (T2D). In contrast to this canonical dichotomy, insulin resistance appears to precede the overt diabetic stage of T1D and to predict its progression, implying that insulin sensitizers may change the course of T1D. However, previous attempts to ameliorate T1D in animal models or patients by insulin sensitizers have largely failed...
March 7, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28266632/specific-cpg-hyper-methylation-leads-to-ankrd26-gene-down-regulation-in-white-adipose-tissue-of-a-mouse-model-of-diet-induced-obesity
#17
Gregory A Raciti, Rosa Spinelli, Antonella Desiderio, Michele Longo, Luca Parrillo, Cecilia Nigro, Vittoria D'Esposito, Paola Mirra, Francesca Fiory, Vincenzo Pilone, Pietro Forestieri, Pietro Formisano, Ira Pastan, Claudia Miele, Francesco Beguinot
Epigenetic modifications alter transcriptional activity and contribute to the effects of environment on the individual risk of obesity and Type 2 Diabetes (T2D). Here, we have estimated the in vivo effect of a fat-enriched diet (HFD) on the expression and the epigenetic regulation of the Ankyrin repeat domain 26 (Ankrd26) gene, which is associated with the onset of these disorders. In visceral adipose tissue (VAT), HFD exposure determined a specific hyper-methylation of Ankrd26 promoter at the -436 and -431 bp CpG sites (CpGs) and impaired its expression...
March 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28263745/exercise-increases-hyper-acetylation-of-histones-on-the-cis-element-of-nrf-1-binding-to-the-mef2a-promoter-implications-on-type-2-diabetes
#18
Jitcy S Joseph, Ademola O Ayeleso, Emmanuel Mukwevho
Exercise brings changes on the chromatin ensuing the upregulation of many genes that confer protection from type 2 diabetes. In type-2 diabetes, critical genes are down-regulated such as those involved in glucose transport (GLUT4, MEF2A) and also oxidative phosphorylation (NRF-1 and its target genes). Recent reports have shown that NRF-1 not only regulate mitochondrial oxidative genes but also controls MEF2A, the main transcription factor for glucose transporter, GLUT4. Such dual control of the two pathways by NRF-1 place it as critical gene in the design of therapeutic modalities much needed to cure or better manage type 2 diabetes...
March 2, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28263721/hepatoprotective-effect-of-7-hydroxycoumarin-against-methyl-glyoxal-toxicity-via-activation-of-nrf2
#19
Dan Li, Na Wang, Jingdong Zhang, Shuren Ma, Zhuangzhuang Zhao, Elizabeth M Ellis
Methyl glyoxal (MG), a major precursor of advanced glycation end-products, has been identified as significant in the progression of several diseases including aging, diabetes and neurodegenerative diseases as well as causing hepatic damages. 7-hydroxycoumarin (7-HC), a natural-occurring derivative of coumarin from fruits and plants, has been reported to exert antioxidant and free radical-scavenging properties, protecting cells from aldehydes and oxidants. In this study, the ability of 7-HC to protect human HepG2 cells against MG-induced toxicity and oxidative stress was investigated...
March 2, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28262618/2-4-chlorobenzyl-amino-4-methyl-1-3-thiazole-5-carboxylic-acid-exhibits-antidiabetic-potential-and-raises-insulin-sensitivity-via-amelioration-of-oxidative-enzymes-and-inflammatory-cytokines-in-streptozotocin-induced-diabetic-rats
#20
Yam Nath Paudel, Md Rahmat Ali, Sadia Shah, Mohd Adil, Md Sayeed Akhtar, Ravisha Wadhwa, Sandhya Bawa, Manju Sharma
Thiazole derivatives are potential candidates for drug development. They can be efficiently synthesized and are extremely active against several diseases, including diabetes. In our present study, we investigated the anti-diabetic, anti-oxidant and anti-inflammatory properties of 2-[(4-Chlorobenzyl) amino]-4-methyl-1,3-thiazole-5-carboxylic acid (BAC) a new thiazole derivative, in a streptozotocin (STZ) induced neonatal model of non-insulin dependent diabetes mellitus (NIDDM) rats. Diabetes was induced by injecting STZ (100mg/kg) intraperitoneally to two days old pups...
March 2, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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