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Diabetes epigenetics

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https://www.readbyqxmd.com/read/28427059/the-burden-of-diabetes-emerging-data
#1
Paola Maffi, Antonio Secchi
In recent times, the global prevalence of diabetes has increased substantially, reaching 8.3% in 2014, which corresponds to 387 million patients. Studies in Europe and USA have shown increased incidence of type 1 Diabetes (T1D) over time at a rate of 3-5% per year. Another most worrying feature of the rapid increase of diabetes is the emergence of type 2 Diabetes (T2D) in children, adolescents, and young adults. The well-known behavioral risks factors and epigenetic mechanisms recently observed require an integrated approach to prevent T2D...
2017: Developments in Ophthalmology
https://www.readbyqxmd.com/read/28425976/prenatal-exposure-to-a-maternal-high-fat-diet-affects-histone-modification-of-cardiometabolic-genes-in-newborn-rats
#2
Bijaya Upadhyaya, Tricia Larsen, Shivon Barwari, Eli J Louwagie, Michelle L Baack, Moul Dey
Infants born to women with diabetes or obesity are exposed to excess circulating fuels during fetal heart development and are at higher risk of cardiac diseases. We have previously shown that late-gestation diabetes, especially in conjunction with a maternal high-fat (HF) diet, impairs cardiac functions in rat-offspring. This study investigated changes in genome-wide histone modifications in newborn hearts from rat-pups exposed to maternal diabetes and HF-diet. Chromatin-immunoprecipitation-sequencing revealed a differential peak distribution on gene promoters in exposed pups with respect to acetylation of lysines 9 and 14 and to trimethylation of lysines 4 and 27 in histone H3 (all, false discovery rate, FDR < 0...
April 20, 2017: Nutrients
https://www.readbyqxmd.com/read/28424732/evidence-for-loss-in-identity-de-differentiation-and-trans-differentiation-of-islet-%C3%AE-cells-in-type-2-diabetes
#3
REVIEW
Chad S Hunter, Roland W Stein
The two main types of diabetes mellitus have distinct etiologies, yet a similar outcome: loss of islet β-cell function that is solely responsible for the secretion of the insulin hormone to reduce elevated plasma glucose toward euglycemic levels. Type 1 diabetes (T1D) has traditionally been characterized by autoimmune-mediated β-cell death leading to insulin-dependence, whereas type 2 diabetes (T2D) has hallmarks of peripheral insulin resistance, β-cell dysfunction, and cell death. However, a growing body of evidence suggests that, especially during T2D, key components of β-cell failure involves: (1) loss of cell identity, specifically proteins associated with mature cell function (e...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28423509/histone-lysine-methyltransferase-g9a-is-a-novel-epigenetic-target-for-the-treatment-of-hepatocellular-carcinoma
#4
Masayuki Yokoyama, Tetsuhiro Chiba, Yoh Zen, Motohiko Oshima, Yuko Kusakabe, Yoshiko Noguchi, Kaori Yuki, Shuhei Koide, Shiro Tara, Atsunori Saraya, Kazumasa Aoyama, Naoya Mimura, Satoru Miyagi, Masanori Inoue, Toru Wakamatsu, Tomoko Saito, Sadahisa Ogasawara, Eiichiro Suzuki, Yoshihiko Ooka, Akinobu Tawada, Masayuki Otsuka, Masaru Miyazaki, Osamu Yokosuka, Atsushi Iwama
Histone H3 lysine 9 dimethylation (H3K9me2) is mainly regulated by the histone lysine methyltransferase G9a and is associated with the repression of transcription. However, both the role of G9a and the significance of H3K9me2 in hepatocellular carcinoma (HCC) cells remain unclear. In this study, we conducted loss-of-function assay of G9a using short-hairpin RNA and pharmacological interference. Knockdown of G9a reduced H3K9me2 levels and impaired both HCC cell growth and sphere formation. However, transforming growth factor β1-induced epithelial mesenchymal transition (EMT) was not suppressed by G9a knockdown...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416029/the-health-outcomes-of-human-offspring-conceived-by-assisted-reproductive-technologies-art
#5
M Chen, L K Heilbronn
Concerns have been raised about the health and development of children conceived by assisted reproductive technologies (ART) since 1978. Controversially, ART has been linked with adverse obstetric and perinatal outcomes, an increased risk of birth defects, cancers, and growth and development disorders. Emerging evidence suggests that ART treatment may also predispose individuals to an increased risk of chronic ageing related diseases such as obesity, type 2 diabetes and cardiovascular disease. This review will summarize the available evidence on the short-term and long-term health outcomes of ART singletons, as multiple pregnancies after multiple embryos transfer, are associated with low birth weight and preterm delivery, which can separately increase risk of adverse postnatal outcomes, and impact long-term health...
April 18, 2017: Journal of Developmental Origins of Health and Disease
https://www.readbyqxmd.com/read/28413926/dusp-1-gene-expression-is-not-regulated-by-promoter-methylation-in-diabetes-associated-cardiac-hypertrophy
#6
Gurinder Bir Singh, Sanskriti Khanna, Satish K Raut, Saurabh Sharma, Rajni Sharma, Madhu Khullar
BACKGROUND: The exact mechanism causing decreased expression of the dual specific phosphatase-1 ( DUSP-1) gene in diabetes-associated cardiac hypertrophy is not known. DNA promoter methylation is often associated with decreased gene expression in many diseases including cardiovascular diseases. So, we investigated whether epigenetic silencing via promoter methylation is involved in the decreased expression of DUSP-1 in diabetes-associated cardiac hypertrophy. METHODS: Real-time polymerase chain reaction (PCR) and Western blotting confirmed the down regulation of the DUSP-1 gene at transcriptional and translational levels...
April 1, 2017: Therapeutic Advances in Cardiovascular Disease
https://www.readbyqxmd.com/read/28413567/differential-adipokine-dna-methylation-and-gene-expression-in-subcutaneous-adipose-tissue-from-adult-offspring-of-women-with-diabetes-in-pregnancy
#7
Azadeh Houshmand-Oeregaard, Ninna S Hansen, Line Hjort, Louise Kelstrup, Christa Broholm, Elisabeth R Mathiesen, Tine D Clausen, Peter Damm, Allan Vaag
BACKGROUND: Offspring of women with diabetes in pregnancy are at increased risk of type 2 diabetes mellitus (T2DM), potentially mediated by epigenetic mechanisms. The adipokines leptin, adiponectin, and resistin (genes: LEP, ADIPOQ, RETN) play key roles in the pathophysiology of T2DM. We hypothesized that offspring exposed to maternal diabetes exhibit alterations in epigenetic regulation of subcutaneous adipose tissue (SAT) adipokine transcription. We studied adipokine plasma levels, SAT gene expression, and DNA methylation of LEP, ADIPOQ, and RETN in adult offspring of women with gestational diabetes (O-GDM, N = 82) or type 1 diabetes (O-T1DM, N = 67) in pregnancy, compared to offspring of women from the background population (O-BP, N = 57)...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28412046/the-epigenetic-mechanism-for-discordance-of-autoimmunity-in-monozygotic-twins
#8
REVIEW
Zhongyuan Xiang, Yuanqing Yang, Christopher Chang, Qianjin Lu
Monozygotic twins share an identical DNA sequence but are not truly "identical". In fact, when it comes to health and disease, they may often display some level of phenotypic discordance. The cause of this discordance is often unknown. Epigenetic modifications such as DNA methylation, histone modification, and microRNAs-mediated regulation regulate gene expression and are sensitive to external stimuli. These modifications may be seen to bridge the gap between genetics and the environment. Over the years, the importance of epigenetics as a primary mechanism for the role that the environment plays in defining phenotype has been increasingly appreciated...
April 12, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28408391/lmna-associated-partial-lipodystrophy-anticipation-of-metabolic-complications
#9
Isabelle Jeru, Camille Vatier, Marie-Christine Vantyghem, Olivier Lascols, Corinne Vigouroux
BACKGROUND: Type-2 familial partial lipodystrophy (FPLD2) is a rare autosomal dominant lipodystrophic disorder due to mutations in LMNA encoding lamin A/C, a key epigenetic regulator. FPLD2 severity is determined by the occurrence of metabolic complications, especially diabetes and hypertriglyceridaemia. We evaluated the disease history and severity over generations. METHODS: This retrospective study of the largest cohort of patients with FPLD2 reported to date investigates 85 patients from 24 families comprising three generations (G1: n=39; G2: n=41; G3: n=5)...
April 13, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/28401680/dna-methylation-and-its-role-in-the-pathogenesis-of-diabetes
#10
REVIEW
Amita Bansal, Sara E Pinney
Although the factors responsible for the recent increase in the prevalence of diabetes worldwide are not entirely known, the morbidity associated with this disease results in substantial health and economic burden on society. Epigenetic modifications, including DNA methylation have been identified as one mechanism by which the environment interacts with the genome and there is evidence that alterations in DNA methylation may contribute to the increased prevalence of both type 1 and type 2 diabetes. This review provides a summary of DNA methylation and its role in gene regulation, and includes descriptions of various techniques to measure site-specific and genome-wide DNA methylation changes...
May 2017: Pediatric Diabetes
https://www.readbyqxmd.com/read/28401169/epigenetic-regulations-in-diabetic-nephropathy
#11
REVIEW
Zeyuan Lu, Na Liu, Feng Wang
Diabetic nephropathy (DN) is a chronic complication of diabetes and the most common cause of end-stage kidney disease. It has been reported that multiple factors are involved in the pathogenesis of DN, while the molecular mechanisms that lead to DN are still not fully understood. Numerous risk factors for the development of diabetic nephropathy have been proposed, including ethnicity and inherited genetic differences. Recently, with the development of high-throughput technologies, there is emerging evidence that suggests the important role of epigenetic mechanisms in the pathogenesis of DN...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28398573/skeletal-muscle-pgc1%C3%AE-1-nucleosome-position-and-260nt-dna-methylation-determine-exercise-response-and-prevent-ectopic-lipid-accumulation-in-men
#12
Sudip Bajpeyi, Jeffrey D Covington, Erin M Taylor, Laura K Stewart, Jose E Galgani, Tara M Henagan
Endurance exercise has been shown to improve lipid oxidation and increase mitochondrial content in skeletal muscle: two features that have shown dependence on increased expression of the PPAR gamma co-activator 1 alpha (PGC1α). It is also hypothesized that exercise related alterations in PGC1α expression occur through epigenetic regulation of nucleosome positioning in association with differential DNA methylation status within the PCG1α promoter. Here we show that when primary human myotubes from obese, type 2 diabetics are exposed to lipolytic stimulus (PFI) in vitro, nucleosome occupancy surrounding the -260 nucleotide (nt) region, a known regulatory DNA methylation site, is reduced...
April 10, 2017: Endocrinology
https://www.readbyqxmd.com/read/28396702/interaction-between-prenatal-pesticide-exposure-and-a-common-polymorphism-in-the-pon1-gene-on-dna-methylation-in-genes-associated-with-cardio-metabolic-disease-risk-an-exploratory%C3%A2-study
#13
Ken Declerck, Sylvie Remy, Christine Wohlfahrt-Veje, Katharina M Main, Guy Van Camp, Greet Schoeters, Wim Vanden Berghe, Helle R Andersen
BACKGROUND: Prenatal environmental conditions may influence disease risk in later life. We previously found a gene-environment interaction between the paraoxonase 1 (PON1) Q192R genotype and prenatal pesticide exposure leading to an adverse cardio-metabolic risk profile at school age. However, the molecular mechanisms involved have not yet been resolved. It was hypothesized that epigenetics might be involved. The aim of the present study was therefore to investigate whether DNA methylation patterns in blood cells were related to prenatal pesticide exposure level, PON1 Q192R genotype, and associated metabolic effects observed in the children...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28396406/flicr-a-long-noncoding-rna-modulates-foxp3-expression-and-autoimmunity
#14
David Zemmour, Alvin Pratama, Scott M Loughhead, Diane Mathis, Christophe Benoist
A combination of transcription factors, enhancers, and epigenetic marks determines the expression of the key transcription factor FoxP3 in regulatory T cells (Tregs). Adding an additional layer of complexity, the long noncoding RNA (lncRNA) Flicr (Foxp3 long intergenic noncoding RNA) is a negative regulator that tunes Foxp3 expression, resulting in a subset of Tregs with twofold- to fivefold-lower levels of FoxP3 protein. The impact of Flicr is particularly marked in conditions of IL-2 deficiency, and, conversely, IL-2 represses Flicr expression...
April 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28383051/dual-inhibiting-oct4-and-akt-potently-suppresses-the-propagation-of-human-cancer-cells
#15
Wenxin Li, Yanwen Zhou, Xiaoqian Zhang, Ying Yang, Songsong Dan, Tong Su, Shiqi She, Weilai Dong, Qingwei Zhao, Jia Jia, Hangping Yao, Min Zheng, Bo Kang, Ying-Jie Wang
AKT serves as an epigenetic modulator that links epigenetic regulation to cell survival and proliferation while the epigenetic mediator OCT4 critically controls stem cell pluripotency and self-renewal. Emerging evidence indicated their complicated interplays in cancer cells and cancer stem cells (CSCs), and inhibiting either one may activate the other. Thus, in this study, we propose a strategy to targeting both factors simultaneously. Firstly, a combination of an OCT4-specific shRNA and the specific AKT inhibitor Akti-1/2 potently suppressed the propagation of human embryonal carcinoma cells, adherent cancer cells and stem-like cancer cells, establishing the proof-of-concept that dual inhibiting OCT4 and AKT can effectively target various cancer cells...
April 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28364255/microrna-184-is-a-downstream-effector-of-albuminuria-driving-renal-fibrosis-in-rats-with-diabetic-nephropathy
#16
Cristina Zanchi, Daniela Macconi, Piera Trionfini, Susanna Tomasoni, Daniela Rottoli, Monica Locatelli, Michael Rudnicki, Jo Vandesompele, Pieter Mestdagh, Giuseppe Remuzzi, Ariela Benigni, Carlamaria Zoja
AIMS/HYPOTHESIS: Renal fibrosis is a common complication of diabetic nephropathy and is a major cause of end-stage renal disease. Despite the suggested link between renal fibrosis and microRNA (miRNA) dysregulation in diabetic nephropathy, the identification of the specific miRNAs involved is still incomplete. The aim of this study was to investigate miRNA profiles in the diabetic kidney and to identify potential downstream targets implicated in renal fibrosis. METHODS: miRNA expression profiling was investigated in the kidneys of 8-month-old Zucker diabetic fatty (ZDF) rats during overt nephropathy...
March 31, 2017: Diabetologia
https://www.readbyqxmd.com/read/28361696/p-hint-hunt-a-deep-parallelized-whole-genome-dna-methylation-detection-tool
#17
Shaoliang Peng, Shunyun Yang, Ming Gao, Xiangke Liao, Jie Liu, Canqun Yang, Chengkun Wu, Wenqiang Yu
BACKGROUND: The increasing studies have been conducted using whole genome DNA methylation detection as one of the most important part of epigenetics research to find the significant relationships among DNA methylation and several typical diseases, such as cancers and diabetes. In many of those studies, mapping the bisulfite treated sequence to the whole genome has been the main method to study DNA cytosine methylation. However, today's relative tools almost suffer from inaccuracies and time-consuming problems...
March 14, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28360945/epigenetic-signatures-of-gestational-diabetes-mellitus-on-cord-blood-methylation
#18
Larissa Haertle, Nady El Hajj, Marcus Dittrich, Tobias Müller, Indrajit Nanda, Harald Lehnen, Thomas Haaf
BACKGROUND: Intrauterine exposure to gestational diabetes mellitus (GDM) confers a lifelong increased risk for metabolic and other complex disorders to the offspring. GDM-induced epigenetic modifications modulating gene regulation and persisting into later life are generally assumed to mediate these elevated disease susceptibilities. To identify candidate genes for fetal programming, we compared genome-wide methylation patterns of fetal cord bloods (FCBs) from GDM and control pregnancies...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28357066/association-of-two-synonymous-splicing-associated-cpg-single-nucleotide-polymorphisms-in-calpain-10-and-solute-carrier-family-2-member-2-with-type-2-diabetes
#19
Maria Karambataki, Andigoni Malousi, Georgios Tzimagiorgis, Constantinos Haitoglou, Aikaterini Fragou, Elisavet Georgiou, Foteini Papadopoulou, Gerasimos E Krassas, Sofia Kouidou
Coding synonymous single nucleotide polymorphisms (SNPs) have attracted little attention until recently. However, such SNPs located in epigenetic, CpG sites modifying exonic splicing enhancers (ESEs) can be informative with regards to the recently verified association of intragenic methylation and splicing. The present study describes the association of type 2 diabetes (T2D) with the exonic, synonymous, epigenetic SNPs, rs3749166 in calpain 10 (CAPN10) glucose transporter (GLUT4) translocator and rs5404 in solute carrier family 2, member 2 (SLC2A2), also termed GLUT2, which, according to prior bioinformatic analysis, strongly modify the splicing potential of glucose transport-associated genes...
February 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28357065/role-of-micrornas-in-the-pathogenesis-of-diabetic-cardiomyopathy
#20
Xinyu Liu, Shixue Liu
The morbidity of diabetes mellitus has been increasing annually. As a progressive metabolic disorder, chronic complications occur in the late stage of diabetes. In addition, cardiovascular diseases account for the major cause of morbidity and mortality among the diabetic population worldwide. Diabetic cardiomyopathy (DCM) is a type of diabetic heart disease. Patients with DCM show symptoms and signs of heart failure while no specific cause, such as coronary disease, hypertension, alcohol consumption, or other structural heart diseases has been identified...
February 2017: Biomedical Reports
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