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methylation diabetes

Agnes A Michalczyk, Edward D Janus, Alisha Judge, Peter R Ebeling, James D Best, Michael J Ackland, Dino Asproloupos, James A Dunbar, M Leigh Ackland
AIM: To investigate epigenomic changes in pregnancy and early postpartum in women with and without type 2 diabetes. METHODS: Dimethylation of histones H3K4, H3K9, H3K27, H3K36 and H3K79 was measured in white blood cells of women at 30 weeks pregnancy, at 8-10 and 20 weeks postpartum and in never-pregnant women. RESULTS: Dimethylation levels of all five histones were different between women in pregnancy and early postpartum compared with never-pregnant women and were different between women with and without type 2 diabetes...
March 21, 2018: Epigenomics
Khaled Elmasry, Riyaz Mohamed, Isha Sharma, Nehal M Elsherbiny, Yutao Liu, Mohamed Al-Shabrawey, Amany Tawfik
To study Hyperhomocysteinemia (HHcy)-induced epigenetic modifications as potential mechanisms of blood retinal barrier (BRB) dysfunction, retinas isolated from three- week-old mice with elevated level of Homocysteine (Hcy) due to lack of the enzyme cystathionine β-synthase ( cbs-/- , cbs+/- and cbs+/+ ), human retinal endothelial cells (HRECs), and human retinal pigmented epithelial cells (ARPE-19) treated with or without Hcy were evaluated for (1) histone deacetylases (HDAC), (2) DNA methylation (DNMT), and (3) miRNA analysis...
February 27, 2018: Oncotarget
Mark F McCarty, James H O'Keefe, James J DiNicolantonio
Background: Glutathione is a key scavenging antioxidant that opposes the proinflammatory signaling of hydrogen peroxide. Boosting cellular glutathione levels may have broad utility in the prevention and treatment of disorders driven by oxidative stress. Supplemental N-acetylcysteine has been employed for this purpose. Could supplemental glycine likewise promote glutathione synthesis? Methods: We conducted a review of the pertinent literature using PubMed. Results: Tissue glycine levels are lower than the glutathione synthase Michaelis constant (Km ) for glycine...
2018: Ochsner Journal
Pennapa Chonpathompikunlert, Phetcharat Boonruamkaew, Wanida Sukketsiri, Pilaiwanwadee Hutamekalin, Morakot Sroyraya
BACKGROUND: Apium graveolens L. is a traditional Chinese medicine prescribed as a treatment for hypertension, gout, and diabetes. This study aimed to determine the neuroprotective effects of A. graveolens extract against a Parkinson's disease (PD) model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in C57BL/6 mice. METHODS: Male C57BL/6 mice treated with MPTP were orally dosed with A. graveolens extract daily for 21 days. Behavioral tests, including a rotarod apparatus, a narrow beam test, a drag test, a grid walk test, a swimming test, and a resting tremor evaluation, were performed...
March 20, 2018: BMC Complementary and Alternative Medicine
Muge Yucel, Osman Akin, Mehmet Cayoren, Ibrahim Akduman, Alagappan Palaniappan, Bo Liedberg, Gurkan Hizal, Fatih Inci, Umit Hakan Yildiz
This study reports on a handheld volatilome analyzer for selective determination of clinically relevant biomarkers in exhaled breath. The sensing platform is based on electrospun polymer nanofiber-multi walled carbon nanotube (MWCNT) sensing micro-channels. Polymer nanofibers of poly(vinylidene fluoride) (PVDF), polystyrene (PS), and poly(methyl methacrylate) (PMMA) incorporated with MWCNT exhibits stable response to interferences of humidity and CO2 and provides selective deformations upon exposure of exhaled breath target volatilomes acetone and toluene, exhibiting correlation to diabetes and lung cancer, respectively...
March 20, 2018: Analytical Chemistry
Te-Sha Tsai, Sonika Tyagi, Justin C St John
STUDY QUESTION: What are the molecular differences between mitochondrial DNA (mtDNA)-deficient and mtDNA-normal oocytes and how does mitochondrial supplementation alter these? SUMMARY ANSWER: Changes to DNA methylation in a 5' cytosine-phosphate-guanine 3' (CpG) island in the mtDNA-specific replication factor (DNA polymerase gamma (POLG)) of mtDNA-deficient oocytes mediates an increase in mtDNA copy number by the 2-cell stage that positively modulates the expression of nuclear genes, which affect cellular and metabolic processes, following autologous mitochondrial supplementation...
March 13, 2018: Human Reproduction
Ximena Corso-Díaz, Catherine Jaeger, Vijender Chaitankar, Anand Swaroop
Complex biological processes, such as organogenesis and homeostasis, are stringently regulated by genetic programs that are fine-tuned by epigenetic factors to establish cell fates and/or to respond to the microenvironment. Gene regulatory networks that guide cell differentiation and function are modulated and stabilized by modifications to DNA, RNA and proteins. In this review, we focus on two key epigenetic changes - DNA methylation and histone modifications - and discuss their contribution to retinal development, aging and disease, especially in the context of age-related macular degeneration (AMD) and diabetic retinopathy...
March 12, 2018: Progress in Retinal and Eye Research
Tinashe Mutize, Zibusiso Mkandla, Bongani B Nkambule
BACKGROUND: DNA methylation (global and gene-specific) has been reported as an epigenetic mechanism that could be involved in the pathogenesis of type 2 diabetes mellitus (T2DM). Furthermore, epigenetic therapy has been suggested as a future possibility for T2DM treatment. Epigenetic changes illustrate the environmental link of the disease. Since some of the epigenetic modifications can be reversed, they could be used as potential therapeutic targets. The aim of the systematic review will be to synthesise the available evidence pertaining to the link between DNA methylation and T2DM...
March 15, 2018: Systematic Reviews
Kun Qian, Hao Hu, Hui Xu, Y George Zheng
Protein arginine methyltransferases (PRMTs) are crucial epigenetic regulators in eukaryotic organisms that serve as histone writers for chromatin remodeling. PRMTs also methylate a variety of non-histone protein substrates to modulate their function and activity. The development of potent PRMT inhibitors has become an emerging and imperative research area in the drug discovery field to provide novel therapeutic agents for treating diseases and as tools to investigate the biological functions of PRMTs. PRMT1 is the major type I enzyme that catalyzes the formation of asymmetric dimethyl arginine, and PRMT1 plays important regulatory roles in signal transduction, transcriptional activation, RNA splicing, and DNA repair...
2018: Signal Transduction and Targeted Therapy
Miguel Fontecha-Barriuso, Diego Martin-Sanchez, Olga Ruiz-Andres, Jonay Poveda, Maria Dolores Sanchez-Niño, Lara Valiño-Rivas, Marta Ruiz-Ortega, Alberto Ortiz, Ana Belén Sanz
Epigenetics refers to heritable changes in gene expression patterns not caused by an altered nucleotide sequence, and includes non-coding RNAs and covalent modifications of DNA and histones. This review focuses on functional evidence for the involvement of DNA and histone epigenetic modifications in the pathogenesis of kidney disease and the potential therapeutic implications. There is evidence of activation of epigenetic regulatory mechanisms in acute kidney injury (AKI), chronic kidney disease (CKD) and the AKI-to-CKD transition of diverse aetiologies, including ischaemia-reperfusion injury, nephrotoxicity, ureteral obstruction, diabetes, glomerulonephritis and polycystic kidney disease...
March 9, 2018: Nephrology, Dialysis, Transplantation
Ning Wang, Yanan Zhu, Min Xie, Lintao Wang, Feiyan Jin, Yihui Li, Qingxin Yuan, Wei De
BACKGROUND/AIMS: The main pathogenic mechanism of diabetes is a decrease in the number of islet beta cells or a decline in their function. Recent studies have shown that pancreatic long noncoding RNAs (lncRNAs) have a high degree of tissue specificity and may be involved in the maintenance of islet cells function and the development of diabetes. The aim of this study was to investigate the molecular regulatory mechanism of mouse maternal expressed gene 3 (Meg3) in insulin biosynthesis in pancreatic islets...
March 6, 2018: Cellular Physiology and Biochemistry
Meghan McGee, Shannon Bainbridge, Bénédicte Fontaine-Bisson
The fetal origins of health and disease framework has identified extremes in fetal growth and birth weight as factors associated with the lifelong generation of chronic diseases such as obesity, diabetes, cardiovascular disease, and hypertension. Maternal nutrition plays a critical role in fetal and placental development, in part by providing the methyl groups required to establish the fetus's genome structure and function, notably through DNA methylation. The goal of this narrative review is to describe the role of maternal dietary methyl donor (methionine, folate, and choline) and cofactor (zinc and vitamins B2, B6, and B12) intake in one-carbon metabolism and DNA methylation in the fetus and placenta, as well as their impacts on fetal growth and lifelong health outcomes, with specific examples in animals and humans...
February 26, 2018: Nutrition Reviews
Ji-Yuan Zhao, Li Yang, Hu-Hu Bai, Jiang-Ping Liu, Zhan-Wei Suo, Xian Yang, Xiao-Dong Hu
Protein tyrosine phosphatase 1B (PTP1B) has been shown to dephosphorylate and inactivate insulin receptors, which contributes to the pathogenesis of diabetes. Neuropathic pain is one of the severe complications that results from diabetic neuropathy. However, whether PTP1B was involved in the development of diabetic neuropathic pain is largely unknown. The current study illustrated that PTP1B was located in spinal cord dorsal horn neurons of Sprague-Dawley rats. Western blot analysis demonstrated that the diabetic neuropathic pain induced by intraperitoneal injection of streptozotocin was associated with an increased protein expression and a dynamic redistribution of spinal PTP1B into excitatory glutamatergic synapses...
March 8, 2018: European Journal of Pharmacology
Vladimir Kepe, Claudio Scafoglio, Jie Liu, William H Yong, Marvin Bergsneider, Sung-Cheng Huang, Jorge R Barrio, Ernest M Wright
A novel glucose transporter, the sodium glucose cotransporter 2 (SGLT2), has been demonstrated to contribute to the demand for glucose by pancreatic and prostate tumors, and its functional activity has been imaged using a SGLT specific PET imaging probe, α-methyl-4-[F-18]fluoro-4-deoxy-D-glucopyaranoside (Me-4FDG). In this study, Me-4FDG PET was extended to evaluate patients with high-grade astrocytic tumors. Me-4FDG PET scans were performed in four patients diagnosed with WHO Grade III or IV astrocytomas and control subjects, and compared with 2-deoxy-2-[F-18]fluoro-D-glucose (2-FDG) PET and magnetic resonance imaging (MRI) of the same subjects...
March 10, 2018: Journal of Neuro-oncology
Zhongjian Cheng, Xinggui Shen, Xiaohua Jiang, Huimin Shan, Maria Cimini, Pu Fang, Yong Ji, Joon Young Park, Konstantinos Drosatos, Xiaofeng Yang, Christopher G Kevil, Raj Kishore, Hong Wang
Insufficient hydrogen sulfide (H2 S) has been implicated in Type 2 diabetic mellitus (T2DM) and hyperhomocysteinemia (HHcy)-related cardiovascular complications. We investigated the role of H2 S in T2DM and HHcy-induced endothelial dysfunction in small mesenteric artery (SMA) of db/db mice fed a high methionine (HM) diet. HM diet (8 weeks) induced HHcy in both T2DM db/db mice and non-diabetic db/+ mice (total plasma Hcy: 48.4 and 31.3 µM, respectively), and aggravated the impaired endothelium-derived hyperpolarization factor (EDHF)-induced endothelium-dependent relaxation to acetylcholine (ACh), determined by the presence of eNOS inhibitor N(ω)-nitro-L-arginine methyl ester (L-NAME) and prostacyclin (PGI2 ) inhibitor indomethacin (INDO), in SMA from db/db mice but not that from db/+ mice...
February 14, 2018: Redox Biology
Reema Abdelkareem Abu Khalaf, Dima Sabbah, Eveen Al-Shalabi, Iyad Al-Sheikh, Ghadeer Albadawi, Ghassan Abu Sheikha
BACKGROUND: Diabetes mellitus is a major worldwide health concern that has several serious complications including retinopathy, neuropathy, nephropathy and macrovascular diseases. OBJECTIVE: Dipeptidyl peptidase-IV (DPP-IV) inhibitors, gliptins, are a new class of antidiabetic agents that potentiates the action of incretins in decreasing the blood glucose levels. METHODS: In the present study, synthesis and characterization of a series of ten N4-sulfonamido-acrylic and phthalamic acid methyl esters (3a-e and 5a-e) were achieved...
March 8, 2018: Current Computer-aided Drug Design
Fangyuan Guo, Dongxue Huang, Wei Zhang, Qinying Yan, Qingliang Yang, Yan Yang, Hanbing Li, Junxian Yun, Weiyong Hong, Gensheng Yang
Elastomers are largely developed for biomedical applications; however, little is reported on them although they are an effective and controllable delivery system for proteins. In the present study, we investigated the pharmacokinetics, biosecurity, and hypoglycemic effect of an insulin-loaded elastomer formulation in diabetic rats. Cylindrical insulin-loaded elastomers were fabricated using a UV cross-linking process based on methyl-acrylic-star-poly(ε-caprolactone-co-D,L-lactide) cyclic ester and methyl-bi-acrylic-poly(ε-caprolactone-b-polyethylene glycol-b-ε-caprolactone) (CLPEGCLMA)...
March 1, 2018: Materials Science & Engineering. C, Materials for Biological Applications
Haiqiang Yao, Shanlan Mo, Ji Wang, Yingshuai Li, Chong-Zhi Wang, Jin-Yi Wan, Zengliang Zhang, Yu Chen, Ranran Sun, Chun-Su Yuan, Xin Liu, Lingru Li, Qi Wang
BACKGROUND/AIMS: Metabolic diseases are leading health concerns in today's global society. In traditional Chinese medicine (TCM), one body type studied is the phlegm-dampness constitution (PC), which predisposes individuals to complex metabolic disorders. Genomic studies have revealed the potential metabolic disorders and the molecular features of PC. The role of epigenetics in the regulation of PC, however, is unknown. METHODS: We analyzed a genome-wide DNA methylation in 12 volunteers using Illumina Infinium Human Methylation450 BeadChip on peripheral blood mononuclear cells (PBMCs)...
March 2, 2018: Cellular Physiology and Biochemistry
Hlaing H Maw, Xingzhong Zeng, Scot Campbell, Mitchell E Taub, Aaron M Teitelbaum
BI 187004, an 11β-hydroxysteroid dehydrogenase 1 (HSD) inhibitor, was administered once daily for 14 days to eight patients with type 2 diabetes mellitus. N-methylation was identified as a major biotransformation pathway. In four patients treated with BI 187004, the plasma exposure of an N-methylbenzimidazole metabolite (M1) was 7 fold higher than the remaining four patients, indicating a substantial degree of metabolic variation. To identify the methyltransferase enzyme(s) responsible for N-methylation, BI 187004 was incubated with human liver microsomes (HLM), human kidney microsomes (HKM), and their respective cytosolic preparations in the presence and absence of isoform-selective chemical inhibitors...
March 7, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Rui Xu, Wenbin Chen, Zhifen Zhang, Yang Qiu, Yong Wang, Bingchang Zhang, Wei Lu
Bone-Marrow Stromal Cells (BMSCs)-derived vascular endothelial cells (VECs) is regarded as an important therapeutic strategy for spinal cord injury, disc degeneration, cerebral ischemic disease and diabetes. The change in DNA methylation level is essential for stem cell differentiation. However, the DNA methylation related mechanisms underlying the endothelial differentiation of BMSCs are not well understood. In this study, DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine (5-aza-dC) significantly elevated the endothelial markers expression (CD31/PECAM1, CD105/ENG, eNOS and VE-cadherin), as well as promoted the capacity of angiogenesis on Matrigel...
March 4, 2018: Gene
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