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https://www.readbyqxmd.com/read/28727822/dna-methylation-of-candidate-genes-in-peripheral-blood-from-patients-with-type-2-diabetes-or-the-metabolic-syndrome
#1
Sanne D van Otterdijk, Alexandra M Binder, Katarzyna Szarc Vel Szic, Julia Schwald, Karin B Michels
INTRODUCTION: The prevalence of type 2 diabetes (T2D) and the metabolic syndrome (MetS) is increasing and several studies suggested an involvement of DNA methylation in the development of these metabolic diseases. This study was designed to investigate if differential DNA methylation in blood can function as a biomarker for T2D and/or MetS. METHODS: Pyrosequencing analyses were performed for the candidate genes KCNJ11, PPARγ, PDK4, KCNQ1, SCD1, PDX1, FTO and PEG3 in peripheral blood leukocytes (PBLs) from 25 patients diagnosed with only T2D, 9 patients diagnosed with T2D and MetS and 11 control subjects without any metabolic disorders...
2017: PloS One
https://www.readbyqxmd.com/read/28725942/l-arginine-supplementation-prevents-allodynia-and-hyperalgesia-in-painful-diabetic-neuropathic-rats-by-normalizing-plasma-nitric-oxide-concentration-and-increasing-plasma-agmatine-concentration
#2
Lusliany J Rondón, M C Farges, N Davin, B Sion, A M Privat, M P Vasson, A Eschalier, C Courteix
PURPOSE: Neuropathic pain is a common diabetic complication. It is characterized by symptoms of spontaneous and stimulus-evoked pain including hyperalgesia and allodynia. L-Arginine is a common precursor of many metabolites of biological interest, in particular, nitric oxide (NO), ornithine, and hence polyamines. In central nervous system, NO, glutamate, and polyamines share an N-methyl-D-aspartate (NMDA) receptor-mediated effect. We hypothesized that a variation in arginine metabolism caused by diabetes may contribute to development and maintenance of neuropathic pain and to the worsening of clinical and biological signs of diabetes...
July 19, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28723729/wnt-signaling-in-cardiovascular-disease-opportunities-and-challenges
#3
Austin Gay, Dwight A Towler
PURPOSE OF REVIEW: Cardiometabolic diseases increasingly afflict our aging, dysmetabolic population. Complex signals regulating low-density lipoprotein receptor-related protein (LRP) and frizzled protein family members - the plasma membrane receptors for the cadre of Wnt polypeptide morphogens - contribute to the control of cardiovascular homeostasis. RECENT FINDINGS: Both canonical (β-catenin-dependent) and noncanonical (β-catenin-independent) Wnt signaling programs control vascular smooth muscle (VSM) cell phenotypic modulation in cardiometabolic disease...
July 18, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28709971/epigenetic-mechanisms-underlying-the-toxic-effects-associated-with-arsenic-exposure-and-the-development-of-diabetes
#4
REVIEW
Fazlullah Khan, Saeideh Momtaz, Kamal Niaz, Fatima Ismail Hassan, Mohammad Abdollahi
BACKGROUND: Exposure to inorganic arsenic (iAs) is a major threat to the human health worldwide. The consumption of arsenic in drinking water and other food products is associated with the risk of development of type-2 diabetes mellitus (T2DM). The available experimental evidence indicates that epigenetic alterations may play an important role in the development of diseases that are linked with exposure to environmental toxicants. iAs seems to be associated with the epigenetic modifications such as alterations in DNA methylation, histone modifications, and micro RNA (miRNA) abundance...
July 11, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28705609/hand-shoulder-and-back-stiffness-in-long-term-type-1-diabetes-cross-sectional-association-with-skin-collagen-advanced-glycation-end-products-the-dialong-study
#5
Kristine Bech Holte, Niels Gunnar Juel, Jens Ivar Brox, Kristian Folkvord Hanssen, Dag Sigurd Fosmark, David R Sell, Vincent M Monnier, Tore Julsrud Berg
AIMS: We aimed to: (i) estimate the prevalence of Dupuytren's disease, trigger finger, carpal tunnel syndrome and frozen shoulder; (ii) assess stiffness of the hand, shoulder and back; and (iii) explore the association of joint stiffness with both long-term HbA1c and collagen advanced glycation end-products (AGEs) in long-term type 1 diabetes mellitus (T1DM). METHODS: Patients with T1DM from 1970 or earlier attending a specialized diabetes center were included in this cross-sectional controlled study...
June 22, 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28704725/simultaneous-estimation-of-lisofylline-and-pentoxifylline-in-rat-plasma-by-high-performance-liquid-chromatography-photodiode-array-detector-and-its-application-to-pharmacokinetics-in-rat
#6
Kishan S Italiya, Saurabh Sharma, Ishit Kothari, Deepak Chitkara, Anupama Mittal
Lisofylline (LSF) is an anti-inflammatory and immunomodulatory agent with proven activity in serious infections associated with cancer chemotherapy, hyperoxia-induced acute lung injury, autoimmune disorders including type-1 diabetes (T1DM) and islet rejection after islet transplantation. It is also an active metabolite of another anti-inflammatory agent, Pentoxifylline (PTX). LSF bears immense therapeutic potential in multiple pharmacological activities and hence appropriate and accurate quantification of LSF is very important...
June 29, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28694663/inhibition-of-n-methyl-n-nitrosourea-induced-gastric-tumorigenesis-by-liuwei-dihuang-pill-in-db-db-mice
#7
Shan Zhuang, Yong-Mei Jian, Yong-Ning Sun
AIM: To investigate the inhibitory effect of Liuwei Dihuang Pill (LDP) on gastric tumorigenesis induced by N-methyl-N-nitrosourea (MNU) in diabetic mice. METHODS: Four-week-old mice were divided into four groups: A, 12 db/m mice treated with MNU and saline, as the non-diabetic control; B, 12 db/db mice treated with MNU and saline, as the diabetic control; C, 12 db/db mice treated with MNU and metformin, as the positive control; and D, 12 db/db mice treated with MNU and LDP...
June 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28693373/prenatal-growth-patterns-and-birthweight-are-associated-with-differential-dna-methylation-and-gene-expression-of-cardiometabolic-risk-genes-in-human-placentas-a-discovery-based-approach
#8
Pao-Yang Chen, Alison Chu, Wen-Wei Liao, Liudmilla Rubbi, Carla Janzen, Fei-Man Hsu, Shanthie Thamotharan, Amit Ganguly, Larry Lam, Dennis Montoya, Matteo Pellegrini, Sherin U Devaskar
Inherent genetic programming and environmental factors affect fetal growth in utero. Epidemiologic data in growth-altered fetuses, either intrauterine growth restricted (IUGR) or large for gestational age (LGA), demonstrate that these newborns are at increased risk of cardiometabolic disease in adulthood. There is growing evidence that the in utero environment leads to epigenetic modification, contributing to eventual risk of developing heart disease or diabetes. In this study, we used reduced representation bisulfite sequencing to examine genome-wide DNA methylation variation in placental samples from offspring born IUGR, LGA, and appropriate for gestational age (AGA) and to identify differential methylation of genes important for conferring risk of cardiometabolic disease...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28689409/global-phosphoproteomic-analysis-of-insulin-akt-mtorc1-s6k-signaling-in-rat-hepatocytes
#9
Yuanyuan Zhang, Yajie Zhang, Yonghao Yu
Insulin resistance is a hallmark of type 2 diabetes. Although multiple genetic and physiological factors interact to cause insulin resistance, deregulated signaling by phosphorylation is a common underlying mechanism. In particular, the specific phosphorylation-dependent regulatory mechanisms and signaling outputs of insulin are poorly understood in hepatocytes, which represents one of the most important insulin-responsive cell types. Using primary rat hepatocytes as a model system, we performed reductive dimethylation (ReDi)-based quantitative mass spectrometric analysis and characterized the phosphoproteome that is regulated by insulin as well as its key downstream kinases including Akt, mTORC1, and S6K...
July 19, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28684632/immunodeficiency-in-pancreatic-adenocarcinoma-with-diabetes-revealed-by-comparative-genomics
#10
Yuanqing Yan, Ruli Gao, Thao L P Trinh, Maria Bartolomeo Grant
Purpose: Pancreatic adenocarcinomas (PAAD) often are not diagnosed until their late stages leaving no effective treatments. Currently immunotherapy provides a promising treatment option against this malignancy. However, a set of immunotherapy agents benefit patients with many types of cancer, but not PAAD. Sharing the origin in the same organ, diabetes and PAAD tend to occur concurrently. We aimed to identify the impact of diabetes on immunotherapy of PAAD by conducting a comparative genomics analysis.    <p>Experimental Design: We analyzed levels 3 PAAD genomics data (RNAseq, miRNAseq, DNA methylation, somatic copy number and somatic mutation) from TCGA and Firehose...
July 6, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28679621/maternal-methyl-donor-and-cofactor-supplementation-in-late-pregnancy-increases-%C3%AE-cell-numbers-at-16-days-of-life-in-growth-restricted-twin-lambs
#11
Siti A Sulaiman, Miles J De Blasio, M Lyn Harland, Kathryn L Gatford, Julie A Owens
Restricted growth before birth (IUGR) increases adult risk of Type 2 diabetes by impairing insulin sensitivity and secretion. Altered fetal one-carbon metabolism is implicated in developmental programming of adult health and disease by IUGR. We therefore evaluated effects of maternal dietary supplementation with methyl donors and cofactors (MMDS), designed to increase fetal supply, on insulin action in the spontaneously IUGR twin lamb. In vivo glucose-stimulated insulin secretion and insulin sensitivity were measured at d 12-14 in singleton controls (CON, n=7 lambs from 7 ewes), twins (IUGR, n=8 lambs from 8 ewes), and twins from ewes that received MMDS (2 g rumen-protected methionine, 300 mg folic acid, 1...
July 5, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28676341/the-circular-rna-interacts-with-stat3-increasing-its-nuclear-translocation-and-wound-repair-by-modulating-dnmt3a-and-mir-17-function
#12
Zhen-Guo Yang, Faryal Mehwish Awan, William W Du, Yan Zeng, Juanjuan Lyu, De Wu, Shaan Gupta, Weining Yang, Burton B Yang
Delayed or impaired wound healing is a major health issue worldwide, especially in patients with diabetes and atherosclerosis. Here we show that expression of the circular RNA circ-Amotl1 accelerated healing process in a mouse excisional wound model. Further studies showed that ectopic circ-Amotl1 increased protein levels of Stat3 and Dnmt3a. The increased Dnmt3a then methylated the promoter of microRNA miR-17, decreasing miR-17-5p levels but increasing fibronectin expression. We found that Stat3, similar to Dnmt3a and fibronectin, was a target of miR-17-5p...
July 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28666800/a-novel-glp-1-gip-dual-agonist-is-more-effective-than-liraglutide-in-reducing-inflammation-and-enhancing-gdnf-release-in-the-mptp-mouse-model-of-parkinson-s-disease
#13
Ziyue Yuan, Dongfang Li, Peng Feng, Guofang Xue, Chenhui Ji, Guanglai Li, Christian Hölscher
Type 2 diabetes mellitus (T2DM) is one of the risk factors for Parkinson's disease (PD). Insulin desensitisation has been observed in the brains of patients, which may promote neurodegeneration. Incretins are a family of growth factors that can re-sensitise insulin signalling. We have previously shown that mimetics of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) have neuroprotective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropypridine (MPTP) mouse model of PD...
June 27, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28656523/discovery-of-5-methyl-2-4-4-methylsulfonyl-benzyl-oxy-phenyl-4-piperazin-1-yl-pyrimidine-derivatives-as-novel-grp119-agonists-for-the-treatment-of-diabetes-and-obesity
#14
Jinying Chen, Zitai Sang, Lu Li, Linhong He, Liang Ma
A series of fused-pyrimidine derivatives were prepared and evaluated for their agonistic activities against human GPR119. Compound 9i showed high potent agonistic activity against HEK293T cells over-expressing human GPR119 and improved glucose tolerance in dose-dependent manner, as well as promoted insulin secretion. In a DIO mice model, 9i also ameliorated the obese-related symptoms by decreasing the body weights without markedly changing food intake, normalized some serum biomarkers, such as ALT, AST, ALP, GLU, CHOL, HDL, and LDL, and exerted therapeutic activity on fat deposition in liver tissue...
June 27, 2017: Molecular Diversity
https://www.readbyqxmd.com/read/28655522/preventive-effect-of-pravastatin-on-the-development-of-hypertension-in-patients-with-hypercholesterolemia-a-post-hoc-analysis-of-the-management-of-elevated-cholesterol-in-the-primary-prevention-group-of-adult-japanese-mega-study
#15
Toshiaki Otsuka, Kyoichi Mizuno, Tomohiro Shinozaki, Yuko Kachi, Haruo Nakamura
BACKGROUND: It remains unclear whether treatment of dyslipidemia with 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (statins) reduces the risk of developing hypertension. OBJECTIVE: In this post-hoc analysis of the Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA) Study, a large-scale primary prevention trial with pravastatin, we examined the preventive effect of pravastatin on the future development of hypertension in patients with hypercholesterolemia...
June 6, 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/28650965/epigenetic-adaptation-of-the-placental-serotonin-transporter-gene-slc6a4-to-gestational-diabetes-mellitus
#16
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
#17
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
#18
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...
August 1, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28618859/sitagliptin-attenuates-endothelial-dysfunction-of-zucker-diabetic-fatty-rats
#19
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
#20
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
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