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Diabetes methylation

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https://www.readbyqxmd.com/read/28650965/epigenetic-adaptation-of-the-placental-serotonin-transporter-gene-slc6a4-to-gestational-diabetes-mellitus
#1
Sofia Blazevic, Marina Horvaticek, Maja Kesic, Peter Zill, Dubravka Hranilovic, Marina Ivanisevic, Gernot Desoye, Jasminka Stefulj
We tested the hypothesis that gestational diabetes mellitus (GDM) alters the DNA methylation pattern of the fetal serotonin transporter gene (SLC6A4), and examined the functional relevance of DNA methylation for regulation of the SLC6A4 expression in the human placenta. The study included 50 mother-infant pairs. Eighteen mothers were diagnosed with GDM and 32 had normal glucose tolerance (NGT). All neonates were of normal birth weight and born at term by planned Cesarean section. DNA and RNA were isolated from samples of tissue collected from the fetal side of the placenta immediately after delivery...
2017: PloS One
https://www.readbyqxmd.com/read/28642028/discovery-of-novel-5-oxa-2-6-diazaspiro-3-4-oct-6-ene-derivatives-as-potent-selective-and-orally-available-somatostatin-receptor-subtype-5-sstr5-antagonists-for-treatment-of-type-2-diabetes-mellitus
#2
Hideki Hirose, Takeshi Yamasaki, Masaki Ogino, Ryo Mizojiri, Yumiko Tamura-Okano, Hiroaki Yashiro, Yo Muraki, Yoshihide Nakano, Jun Sugama, Akito Hata, Shinji Iwasaki, Masanori Watanabe, Tsuyoshi Maekawa, Shizuo Kasai
Somatostatin receptor subtype 5 (SSTR5) has emerged as a novel attractive drug target for type 2 diabetes mellitus. Starting from N-benzyl azetidine derivatives 1 and 2 as in-house hit compounds, we explored the introduction of a carboxyl group into the terminal benzene of 1 to enhance SSTR5 antagonistic activity by the combination of the substituents at the 3-position of the isoxazoline. Incorporation of a carboxyl group at the 4-position of the benzene ring resulted in a significant enhancement in potency, however, the 4-benzoic acid derivative 10c exhibited moderate human ether-a-go-go related gene (hERG) inhibitory activity...
June 9, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28624351/inhibitory-effect-of-vitamin-b3-against-glycation-and-reactive-oxygen-species-production-in-hsa-an-in%C3%A2-vitro-approach
#3
K M Abdullah, Faizan Abul Qais, Iqbal Ahmad, Imrana Naseem
Hyperglycaemia is a key factor for the formation of advanced glycated endproducts (AGEs). Inhibition of glycation may play key role in minimizing the diabetes related complications. We have tried to explore the glucose and methyl glyoxal mediated glycation and antiglycation activity of niacin using human serum albumin as model protein. Protein was incubated with glucose for 28 days at physiological temperature to achieve glycation. Antiglycation activity was evaluated by assessing free lysine, carbonyl content, AGE specific fluorescence...
June 15, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28618859/sitagliptin-attenuates-endothelial-dysfunction-of-zucker-diabetic-fatty-rats
#4
Huanyuan Wang, Yi Zhou, Zhiying Guo, Yu Dong, Jiahui Xu, Haixia Huang, Huirong Liu, Wen Wang
Although the contributions of sitagliptin to endothelial function in diabetes mellitus were previously reported, the potential mechanisms still remain undefined. Our research was intended to explore the underlying mechanisms of protective effects of sitagliptin treatment on endothelial dysfunction in Zucker diabetic fatty (ZDF) rats. Male lean nondiabetic Zucker rats were used as control and male obese ZDF rats were randomly divided into ZDF and ZDF + sitagliptin groups. The significant decrease in endothelium-dependent relaxation induced by acetylcholine was observed in mesenteric arteries and thoracic aorta rings of ZDF rats...
January 1, 2017: Journal of Cardiovascular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28611866/association-of-cognitive-impairment-in-patients-on-3-hydroxy-3-methyl-glutaryl-coa-reductase-inhibitors
#5
Satyajeet Roy, Joshua Louis Weinstock, Allyse Sachiko Ishino, Jefferson Felix Benites, Samantha Rachel Pop, Christopher David Perez, Edvard Adrian Gumbs, Jennifer Ann Rosenbaum, Mary Kate Roccato, Hely Shah, Gabriela Contino, Krystal Hunter
BACKGROUND: Atherosclerotic cardiovascular diseases are the leading cause of death in the United States. A reduction in cholesterol with 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors (statin) significantly reduces mortality and morbidity. Statins may be associated with cognitive impairment or dementia. Our aim was to study the association of cognitive impairment or dementia in patients who were on a statin. METHODS: Electronic medical records of 3,500 adult patients in our suburban internal medicine office were reviewed...
July 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28608766/wsf-p-1-a-novel-ampk-activator-promotes-adiponectin-multimerization-in-3t3-l1-adipocytes
#6
Yao Wang, Yudian Zhang, Yunyun Wang, Han Peng, Jian Rui, Zhijie Zhang, Shifa Wang, Zhen Li
Adiponectin, an adipokine with insulin-sensitizing effect, is secreted from adipocytes into circulation as high, medium, and low molecular weight forms (HMW, MMW, and LMW). The HMW adiponectin oligomers possess the most potent insulin-sensitizing activity. WSF-P-1(N-methyl-1,2,3,4,5,6-hexahydro-1,1,5,5-tetramethyl-7H-2,4α-methanonaphthalen-7-amine) is derived from natural sesquiterpene longifolene by chemical modifications. We found that WSF-P-1 activates AMPK in both 3T3-L1 adipocytes and 293T cells in this study...
June 13, 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28607629/the-impact-of-environmental-factors-in-influencing-epigenetics-related-to-oxidative-states-in-the-cardiovascular-system
#7
REVIEW
Francesco Angelini, Francesca Pagano, Antonella Bordin, Marika Milan, Isotta Chimenti, Mariangela Peruzzi, Valentina Valenti, Antonino Marullo, Leonardo Schirone, Silvia Palmerio, Sebastiano Sciarretta, Colin E Murdoch, Giacomo Frati, Elena De Falco
Oxidative states exert a significant influence on a wide range of biological and molecular processes and functions. When their balance is shifted towards enhanced amounts of free radicals, pathological phenomena can occur, as the generation of reactive oxygen species (ROS) in tissue microenvironment or in the systemic circulation can be detrimental. Epidemic chronic diseases of western societies, such as cardiovascular disease, obesity, and diabetes correlate with the imbalance of redox homeostasis. Current advances in our understanding of epigenetics have revealed a parallel scenario showing the influence of oxidative stress as a major regulator of epigenetic gene regulation via modification of DNA methylation, histones, and microRNAs...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28603417/glucose-and-temperature-sensitive-nanoparticles-for-insulin-delivery
#8
Jun-Zi Wu, Gareth R Williams, He-Yu Li, Dongxiu Wang, Huanling Wu, Shu-De Li, Li-Min Zhu
Glucose- and temperature-sensitive polymers of a phenylboronic acid derivative and diethylene glycol dimethacrylate (poly(3-acrylamidophenyl boronic acid-b-diethylene glycol methyl ether methacrylate); p(AAPBA-b-DEGMA)) were prepared by reversible addition-fragmentation chain transfer polymerization. Successful polymerization was evidenced by (1)H nuclear magnetic resonance and infrared spectroscopy, and the polymers were further explored in terms of their glass transition temperatures and by gel permeation chromatography (GPC)...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28601507/synthesis-and-pharmacological-evaluation-of-glycine-amide-derivatives-as-novel-vascular-adhesion-protein-1-inhibitors-without-cyp3a4-and-cyp2c19-inhibition
#9
Susumu Yamaki, Yuji Koga, Akira Nagashima, Mitsuhiro Kondo, Yoshiaki Shimada, Keitaro Kadono, Ayako Moritomo, Kosei Yoshihara
Vascular adhesion protein-1 (VAP-1) is a promising therapeutic target for the treatment of diabetic nephropathy. Here, we conducted optimization studies of our lead compound 1, which we previously reported as a novel VAP-1 inhibitor, to enhance the inhibition of human VAP-1 and to reduce CYP3A4 and CYP2C19 inhibition. As a result, we identified 3-chloro-4-{4-[5-(3-{[glycyl(methyl)amino]methyl}phenyl)pyrimidin-2-yl]piperazin-1-yl}benzoic acid (17h) as a novel orally active VAP-1 inhibitor, with 14-fold increased human VAP-1 inhibitory activity compared to 1, without CYP3A4 and CYP2C19 inhibition...
May 31, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28599239/synthesis-structural-elucidation-antioxidant-ct-dna-binding-and-molecular-docking-studies-of-novel-chloroquinoline-derivatives-promising-antioxidant-and-anti-diabetic-agents
#10
S Murugavel, C S Jacob Prasanna Stephen, R Subashini, Dhanabalan AnanthaKrishnan
The synthesized novel chloroquinoline derivatives 1-(2-chloro-4-phenylquinolin-3-yl)ethanone (CPQE), 1-(2,6-dichloro-4-phenylquinolin-3-yl)ethanone (DCPQE), methyl 2,6-dichloro-4-phenylquinoline-3-carboxylate (MDCPQC),methyl 2-chloro-4-methylquinoline-3-carboxylate (MCMQC) were subjected to the elementary analysis like FT-IR, NMR and Mass spectra using GCMS. Also, single crystal X-ray diffraction study was executed for the compound MDCPQC. The crystal packing is stabilized by C-H…π and π-π interactions and also Chlorine-Chlorine short intermolecular contacts generating a three-dimensional supramolecular network...
June 1, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28598817/the-shortening-of-leukocyte-telomere-length-relates-to-dna-hypermethylation-of-line-1-in-type-2-diabetes-mellitus
#11
Yue Wu, Wei Cui, Donghong Zhang, Wei Wu, Zhuo Yang
BACKGROUND: We aim to investigate the cross-talking of leukocyte telomere length (LTL) and DNA methylation of LINE-1 in type 2 diabetes mellitus (T2DM). RESULTS: LTL (ratio of the copy number of telomere [T] repeats to that of a single [S] gene) was significantly shortened in T2DM compared with controls (0.94 ± 0.41 vs. 1.14 ± 0.48, P < 0.001), and decreased steadily with age in both controls and T2DM. Conversely, significant increase of LINE-1 DNA methylation was found in T2DM compared with controls (49...
May 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28598424/raptor-regulates-functional-maturation-of-murine-beta-cells
#12
Qicheng Ni, Yanyun Gu, Yun Xie, Qinglei Yin, Hongli Zhang, Aifang Nie, Wenyi Li, Yanqiu Wang, Guang Ning, Weiqing Wang, Qidi Wang
Diabetes is associated with beta cell mass loss and islet dysfunctions. mTORC1 regulates beta cell survival, proliferation and function in physiological and pathological conditions, such as pregnancy and pancreatectomy. Here we show that deletion of Raptor, which is an essential component of mTORC1, in insulin-expressing cells promotes hypoinsulinemia and glucose intolerance. Raptor-deficient beta cells display reduced glucose responsiveness and exhibit a glucose metabolic profile resembling fetal beta cells...
June 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28597969/the-role-of-epigenetic-regulation-and-pluripotency-related-micrornas-in-differentiation-of-pancreatic-stem-cells-to-beta-cells
#13
Ediz Coskun, Merve Ercin, Selda Gezginci-Oktayoglu
In this study, we aimed to research class-I HDACs and glucose on differentiation of pancreatic islet derived mesenchymal stem cells (PI-MSCs) to beta cells. Beta cell differentiation determined by flow cytometric analysis and gene expression levels of PDX1, PAX4, PAX6, NKX6.1, NGN3, INS2, and GLUT2. The valproic acid, is an inhibitor of class I HDACs, caused the highest beta cell differentiation in PI-MSCs. However, the cells in this group were at early stages of differentiation. Glucose co-administration to this group carried the differentiation to higher levels, but these newly formed beta cells were not functional...
June 9, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28596534/circulating-3-carboxy-4-methyl-5-propyl-2-furanpropanoic-acid-cmpf-levels-are-associated-with-hyperglycemia-and-%C3%AE-cell-dysfunction-in-a-chinese-population
#14
Shan Zhang, Peihong Chen, Hua Jin, Jufen Yi, Xinmiao Xie, Meili Yang, Ting Gao, Lili Yang, Cheng Hu, Xueli Zhang, Xuemei Yu
Several recent clinical studies have suggested that the levels of circulating 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) are significantly higher in patients with gestational diabetes mellitus (GDM), impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM). This study recruited a total of 516 participants. The following patient populations were enrolled: 99 newly diagnosed cases with T2DM, 219 cases with prediabetes [82 with isolated impaired glucose tolerance (I - IGT), 66 with isolated impaired fasting glucose (I - IFG) and 71 with impaired glucose tolerance and impaired fasting glucose (IGT + IFG)], and 198 cases with normal glucose tolerance [NGT, including 99 first-degree relatives of type 2 diabetes patients (FDRs) and 99 non-FDRs]...
June 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28586827/genome-wide-pleiotropy-between-parkinson-disease-and-autoimmune-diseases
#15
Aree Witoelar, Iris E Jansen, Yunpeng Wang, Rahul S Desikan, J Raphael Gibbs, Cornelis Blauwendraat, Wesley K Thompson, Dena G Hernandez, Srdjan Djurovic, Andrew J Schork, Francesco Bettella, David Ellinghaus, Andre Franke, Benedicte A Lie, Linda K McEvoy, Tom H Karlsen, Suzanne Lesage, Huw R Morris, Alexis Brice, Nicholas W Wood, Peter Heutink, John Hardy, Andrew B Singleton, Anders M Dale, Thomas Gasser, Ole A Andreassen, Manu Sharma
Importance: Recent genome-wide association studies (GWAS) and pathway analyses supported long-standing observations of an association between immune-mediated diseases and Parkinson disease (PD). The post-GWAS era provides an opportunity for cross-phenotype analyses between different complex phenotypes. Objectives: To test the hypothesis that there are common genetic risk variants conveying risk of both PD and autoimmune diseases (ie, pleiotropy) and to identify new shared genetic variants and their pathways by applying a novel statistical framework in a genome-wide approach...
June 5, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28580281/glucagon-like-peptide-2-promotes-gallbladder-refilling-via-a-tgr5-independent-glp-2r-dependent-pathway
#16
Bernardo Yusta, Dianne Matthews, Grace B Flock, John R Ussher, Brigitte Lavoie, Gary M Mawe, Daniel J Drucker
OBJECTIVE: Glucagon-like peptides (GLPs) are secreted from enteroendocrine cells in response to nutrients and bile acids and control metabolism via actions on structurally-related yet distinct G protein coupled receptors. GLP-1 regulates gut motility, appetite, islet function, and glucose homeostasis, whereas GLP-2 enhances intestinal nutrient absorption. GLP-1R agonists are used to treat diabetes and obesity, and a GLP-2R agonist is approved to treat short bowel syndrome. Unexpectedly, reports of gallbladder disease have been associated with the use of both GLP-1R and GLP-2R agonists and after bariatric surgery, although the mechanisms remain unknown...
June 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28580279/brown-adipose-tissue-bat-specific-vaspin-expression-is-increased-after-obesogenic-diets-and-cold-exposure-and-linked-to-acute-changes-in-dna-methylation
#17
Juliane Weiner, Kerstin Rohde, Kerstin Krause, Konstanze Zieger, Nora Klöting, Susan Kralisch, Peter Kovacs, Michael Stumvoll, Matthias Blüher, Yvonne Böttcher, John T Heiker
OBJECTIVE: Several studies have demonstrated anti-diabetic and anti-obesogenic properties of visceral adipose tissue-derived serine protease inhibitor (vaspin) and so evoked its potential use for treatment of obesity-related diseases. The aim of the study was to unravel physiological regulators of vaspin expression and secretion with a particular focus on its role in brown adipose tissue (BAT) biology. METHODS: We analyzed the effects of obesogenic diets and cold exposure on vaspin expression in liver and white and brown adipose tissue (AT) and plasma levels...
June 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28572628/adipose-tissue-dysfunction-as-a-central-mechanism-leading-to-dysmetabolic-obesity-triggered-by-chronic-exposure-to-p-p-dde
#18
Diogo Pestana, Diana Teixeira, Manuela Meireles, Cláudia Marques, Sónia Norberto, Carla Sá, Virgínia C Fernandes, Luísa Correia-Sá, Ana Faria, Luísa Guardão, João T Guimarães, Wendy N Cooper, Ionel Sandovici, Valentina F Domingues, Cristina Delerue-Matos, Rosário Monteiro, Miguel Constância, Conceição Calhau
Endocrine-disrupting chemicals such as p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), are bioaccumulated in the adipose tissue (AT) and have been implicated in the obesity and diabetes epidemic. Thus, it is hypothesized that p,p'-DDE exposure could aggravate the harm of an obesogenic context. We explored the effects of 12 weeks exposure in male Wistar rats' metabolism and AT biology, assessing a range of metabolic, biochemical and histological parameters. p,p'-DDE -treatment exacerbated several of the metabolic syndrome-accompanying features induced by high-fat diet (HF), such as dyslipidaemia, glucose intolerance and hypertension...
June 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28571543/aspartame-should-individuals-with-type-ii-diabetes-be-taking-it
#19
Arbind Kumar Choudhary
BACKGROUND: Individuals with type II diabetes (T2D) have to manage blood glucose levels to sustain health and longevity. Artificial sweeteners (including aspartame) are suggested sugar alternatives for these individuals. The safety of aspartame in particular, has long been the centre of debate. Although it is such a controversial product, many clinicians recommend its use to T2D patients, during a controlled diet and as part of an intervention strategy. Aspartame is 200 times sweeter than sugar and has a negligible effect on blood glucose levels, and it is suggested for use so that T2D can control carbohydrate intake and blood glucose levels...
May 31, 2017: Current Diabetes Reviews
https://www.readbyqxmd.com/read/28568316/influence-of-diabetes-on-plasma-pharmacokinetics-and-brain-bioavailability-of-grape-polyphenols-and-their-phase-ii-metabolites-in-the-zucker-diabetic-fatty-rat
#20
Tzu-Ying Chen, Mario G Ferruzzi, Qing-Li Wu, James E Simon, Stephen T Talcott, Jun Wang, Lap Ho, George Todd, Bruce Cooper, Giulio M Pasinetti, Elsa M Janle
SCOPE: The effect of diabetes on the pharmacokinetics, bioavailability and brain distribution of grape polyphenols and select metabolites was studied in the Zucker diabetic fatty (ZDF) rat model. METHODS AND RESULTS: (ZDF) rats and their lean controls (LN) were dosed with a Standardized Grape Polyphenol (SGP) Mixture consisting of grape seed extract, Concord grape juice and resveratrol (RES) by oral gavage for 10 days. An 8 hour pharmacokinetic study was performed...
June 1, 2017: Molecular Nutrition & Food Research
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