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histone deacetylase diabetes

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https://www.readbyqxmd.com/read/28109123/sodium-butyrate-protects-against-high-fat-diet-induced-cardiac-dysfunction-and-metabolic-disorders-in-type-ii-diabetic-mice
#1
Ling Zhang, Jianfeng Du, Naohiro Yano, Hao Wang, Yu Tina Zhao, Dubielecka-Szczerba Patricia, Shougang Zhuang, Eugene Y Chin, Gangjian Qin, Ting C Zhao
Histone deacetylases are recently identified to act as key regulators for cardiac pathophysiology and metabolic disorders. However, the function of histone deacetylase (HDAC) in controlling cardiac performance in type II diabetes and obesity remains unknown. Here we determine whether HDAC inhibition attenuates high fat diet (HFD)-induced cardiac dysfunction and improves metabolic features. Adult mice were fed with either HFD or standard chow food for 24 weeks. Starting at 12 weeks, mice were divided into four groups randomly, in which sodium butyrate (1%), a potent HDAC inhibitor, was provided to chow and HFD-fed mice in drinking water, respectively...
January 21, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28106794/a-thoroughly-validated-virtual-screening-strategy-for-discovery-of-novel-hdac3-inhibitors
#2
Huabin Hu, Jie Xia, Dongmei Wang, Xiang Simon Wang, Song Wu
Histone deacetylase 3 (HDAC3) has been recently identified as a potential target for the treatment of cancer and other diseases, such as chronic inflammation, neurodegenerative diseases, and diabetes. Virtual screening (VS) is currently a routine technique for hit identification, but its success depends on rational development of VS strategies. To facilitate this process, we applied our previously released benchmarking dataset, i.e., MUBD-HDAC3 to the evaluation of structure-based VS (SBVS) and ligand-based VS (LBVS) combinatorial approaches...
January 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27991918/dissociation-of-muscle-insulin-sensitivity-from-exercise-endurance-in-mice-by-hdac3-depletion
#3
Sungguan Hong, Wenjun Zhou, Bin Fang, Wenyun Lu, Emanuele Loro, Manashree Damle, Guolian Ding, Jennifer Jager, Sisi Zhang, Yuxiang Zhang, Dan Feng, Qingwei Chu, Brian D Dill, Henrik Molina, Tejvir S Khurana, Joshua D Rabinowitz, Mitchell A Lazar, Zheng Sun
Type 2 diabetes and insulin resistance are associated with reduced glucose utilization in the muscle and poor exercise performance. Here we find that depletion of the epigenome modifier histone deacetylase 3 (HDAC3) specifically in skeletal muscle causes severe systemic insulin resistance in mice but markedly enhances endurance and resistance to muscle fatigue, despite reducing muscle force. This seemingly paradoxical phenotype is due to lower glucose utilization and greater lipid oxidation in HDAC3-depleted muscles, a fuel switch caused by the activation of anaplerotic reactions driven by AMP deaminase 3 (Ampd3) and catabolism of branched-chain amino acids...
December 19, 2016: Nature Medicine
https://www.readbyqxmd.com/read/27989964/histone-acetylation-of-glucose-induced-thioredoxin-interacting-protein-gene-expression-in-pancreatic-islets
#4
Pradeep Bompada, David Atac, Cheng Luan, Robin Andersson, Judit Domènech Omella, Emilia Ottosson Laakso, Jason Wright, Leif Groop, Yang De Marinis
Thioredoxin-interacting protein (TXNIP) has been shown to be associated with glucose-induced deterioration of pancreatic beta cell function in diabetes. However, whether epigenetic mechanisms contribute to the regulation of TXNIP gene expression by glucose is not clear. Here we studied how glucose exerts its effect on TXNIP gene expression via modulation of histone acetylation marks. To achieve this, we applied clustered regularly interspaced short palindromic repeats/Cas9 (CRISPR/Cas9) to knock out histone acetyltransferase (HAT) p300 in a rat pancreatic beta cell line INS1 832/13...
October 29, 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27928959/potential-application-of-5-aryl-substituted-2-amino-benzamide-type-of-hdac1-2-selective-inhibitors-to-pharmaceuticals
#5
Shinichi Uesato, Yoshiyuki Hirata, Tsutomu Sasaki
Diverse histone deacetylase (HDAC) inhibitors have been developed to date. They control not only histone modification but also gene expression of diverse proteins and thus are expected to provide useful therapeutic effects on various diseases, including cancers, psychiatric and cognitive disorders and neurodegenerative diseases, as well as cardiovascular and diabetic diseases. Some isoform-nonselective HDAC inhibitors have been successfully used for clinical treatments of the haematological malignancies, including advanced forms of cutaneous T-cell lymphoma, refractory peripheral T-cell lymphoma and multiple myeloma...
December 8, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27904654/augmentation-of-histone-deacetylase-3-hdac3-epigenetic-signature-at-the-interface-of-proinflammation-and-insulin-resistance-in-patients-with-type-2-diabetes
#6
Chandrakumar Sathishkumar, Paramasivam Prabu, Mahalingam Balakumar, Raji Lenin, Durai Prabhu, Ranjith Mohan Anjana, Viswanathan Mohan, Muthuswamy Balasubramanyam
BACKGROUND: A role of proinflammation has been implicated in the pathogenesis of diabetes, but the up-stream regulatory signals and molecular signatures are poorly understood. While histone modifications such as changes in histone deacetylase (HDAC) are emerging as novel epigenetic biomarkers, there is lack of studies to demonstrate their clinical relevance in diabetes. Therefore, we investigated the extent of HDAC machinery and inflammatory signals in peripheral blood mononuclear cells (PBMCs) from patients with type 2 diabetes mellitus (T2DM) compared to control subjects...
2016: Clinical Epigenetics
https://www.readbyqxmd.com/read/27904046/cocl2-decreases-ec-sod-expression-through-histone-deacetylation-in-cos7-cells
#7
Shuhei Hattori, Tetsuro Kamiya, Hirokazu Hara, Masayuki Ninomiya, Mamoru Koketsu, Tetsuo Adachi
Extracellular-superoxide dismutase (EC-SOD), one of the SOD isozymes, is negatively regulated under hypoxic conditions, and decreases in its expression may exacerbate vascular diseases. Moreover, epigenetics, such as DNA methylation and histone modifications, are known to play a critical role in the progression of cancer, type 2 diabetes, and atherosclerosis. We previously investigated the involvement of reactive oxygen species (ROS) and p38 mitogen-activated protein kinase (MAPK) in decreases in EC-SOD expression in hypoxic COS7 cells; however, the role of epigenetics in this process currently remains unknown...
2016: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27901066/greater-efficacy-of-atorvastatin-versus-a-non-statin-lipid-lowering-agent-against-renal-injury-potential-role-as-a-histone-deacetylase-inhibitor
#8
Ravi Shankar Singh, Dharmendra Kumar Chaudhary, Aradhana Mohan, Praveen Kumar, Chandra Prakash Chaturvedi, Carolyn M Ecelbarger, Madan M Godbole, Swasti Tiwari
Statins, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors have been shown to improve diabetic nephropathy. However, whether they provide protection via Histone deacetylases (HDAC) inhibition is not clear. We conducted a comparative evaluation of Atorvastatin (AT) versus the non-statin cholesterol-lowering drug, Ezetimibe (EZT) on severity of diabetic nephropathy. Streptozotocin-treated male Wistar rats were fed a cholesterol-supplemented diet and gavaged daily with vehicle, AT or EZT. Control rats received normal diet and gavaged vehicle (n = 8-9/group)...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27799462/sodium-butyrate-activates-nrf2-to-ameliorate-diabetic-nephropathy-possibly-via-inhibition-of-hdac
#9
Wenpeng Dong, Ye Jia, Xiuxia Liu, Huan Zhang, Tie Li, Wenlin Huang, Xudong Chen, Fuchun Wang, Weixia Sun, Hao Wu
Oxidative stress contributes to the pathogenesis of diabetic nephropathy (DN). Nuclear factor erythroid 2-related factor 2 (NRF2) plays a key role in cellular defense against oxidative stress. NRF2 activators have shown promising preventive effects on DN. Sodium butyrate (NaB) is a known activator of NRF2. However, it is unknown whether NRF2 is required for NaB protection against DN. Therefore, streptozotocin-induced diabetic C57BL/6 Nrf2 knockout and their wild-type mice were treated in the presence or absence of NaB for 20 weeks...
2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/27796421/hdac7-is-overexpressed-in-human-diabetic-islets-and-impairs-insulin-secretion-in-rat-islets-and-clonal-beta-cells
#10
Mahboubeh Daneshpajooh, Karl Bacos, Madhusudhan Bysani, Annika Bagge, Emilia Ottosson Laakso, Petter Vikman, Lena Eliasson, Hindrik Mulder, Charlotte Ling
AIMS/HYPOTHESIS: Pancreatic beta cell dysfunction is a prerequisite for the development of type 2 diabetes. Histone deacetylases (HDACs) may affect pancreatic endocrine function and glucose homeostasis through alterations in gene regulation. Our aim was to investigate the role of HDAC7 in human and rat pancreatic islets and clonal INS-1 beta cells (INS-1 832/13). METHODS: To explore the role of HDAC7 in pancreatic islets and clonal beta cells, we used RNA sequencing, mitochondrial functional analyses, microarray techniques, and HDAC inhibitors MC1568 and trichostatin A...
January 2017: Diabetologia
https://www.readbyqxmd.com/read/27649243/antioxidant-rich-extract-from-plantaginis-semen-ameliorates-diabetic-retinal-injury-in-a-streptozotocin-induced-diabetic-rat-model
#11
Thing-Fong Tzeng, Wayne Young Liu, Shorong-Shii Liou, Tang-Yao Hong, I-Min Liu
Plantaginis semen, the dried ripe seed of Plantago asiatica L. or Plantago depressa Willd. (Plantaginaceae), has been traditionally used to treat blurred vision in Asia. The aim of this work was to investigate the effect of plantaginis semen ethanol extract (PSEE) on the amelioration of diabetic retinopathy (DR) in streptozotocin (STZ)-diabetic rats. PSEE has abundant polyphenols with strong antioxidant activity. PSEE (100, 200 or 300 mg/kg) was oral administrated to the diabetic rats once daily consecutively for 8 weeks...
September 18, 2016: Nutrients
https://www.readbyqxmd.com/read/27634872/mitochondrial-aldehyde-dehydrogenase-obliterates-insulin-resistance-induced-cardiac-dysfunction-through-deacetylation-of-pgc-1%C3%AE
#12
Nan Hu, Jun Ren, Yingmei Zhang
Insulin resistance contributes to the high prevalence of type 2 diabetes mellitus, leading to cardiac anomalies. Emerging evidence depicts a pivotal role for mitochondrial injury in oxidative metabolism and insulin resistance. Mitochondrial aldehyde dehydrogenase (ALDH2) is one of metabolic enzymes detoxifying aldehydes although its role in insulin resistance remains elusive. This study was designed to evaluate the impact of ALDH2 overexpression on insulin resistance-induced myocardial damage and mechanisms involved with a focus on autophagy...
September 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27633396/silencing-of-histone-deacetylase-9-expression-in-podocytes-attenuates-kidney-injury-in-diabetic-nephropathy
#13
Feng Liu, Ming Zong, Xiaofei Wen, Xuezhu Li, Jun Wang, Yi Wang, Wei Jiang, Xiaojun Li, Zhongliang Guo, Hualin Qi
Podocyte dysfunction is important in the onset and development of diabetic nephropathy (DN). Histone deacetylases (HDACs) have been recently proved to play critical roles in the pathogenesis of DN. As one subtype of the class IIa HDACs, HDAC9 is capable to repress/de-repress their target genes in tumor, inflammation, atherosclerosis and metabolic diseases. In the present study, we investigate whether HDAC9 is involved in the pathophysiologic process of DN, especially the podocyte injury. Firstly, we explored the expression patterns and localization of HDAC9 and found that HDAC9 expression was significantly up-regulated in high glucose (HG)-treated mouse podocytes, as well as kidney tissues from diabetic db/db mice and patients with DN...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27623388/imbalance-between-hdac-and-hat-activities-drives-aberrant-stat1-myd88-expression-in-macrophages-from-type-1-diabetic-mice
#14
Luciano Ribeiro Filgueiras, Stephanie L Brandt, Theresa Raquel de Oliveira Ramalho, Sonia Jancar, C Henrique Serezani
AIMS: To investigate the hypothesis that alteration in histone acetylation/deacetylation triggers aberrant STAT1/MyD88 expression in macrophages from diabetics. Increased STAT1/MyD88 expression is correlated with sterile inflammation in type 1 diabetic (T1D) mice. METHODS: To induce diabetes, we injected low-doses of streptozotocin in C57BL/6 mice. Peritoneal or bone marrow-differentiated macrophages were cultured in 5mM (low) or 25mM (high glucose). ChIP analysis of macrophages from nondiabetic or diabetic mice was performed to determine acetylation of lysine 9 in histone H3 in MyD88 and STAT1 promoter regions...
August 7, 2016: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/27620069/histone-deacetylase-inhibitors-future-therapeutics-for-insulin-resistance-and-type-2-diabetes
#15
Sorabh Sharma, Rajeev Taliyan
Insulin resistance is a common feature of obesity and predisposes the affected individuals to a variety of pathologies, including type 2 diabetes mellitus (T2DM), dyslipidemias, hypertension, cardiovascular disease etc. Insulin resistance is the primary cause of T2DM and it occurs many years before the disease onset. Although Thiazolidinediones (TZDs) such as rosiglitazone and pioglitazone are outstanding insulin sensitizers and are in clinical use since 1990s, however, their serious side effects such as heart attack and bladder cancer have limited their utilization...
September 9, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27617745/histone-deacetylase-inhibition-restores-retinal-pigment-epithelium-function-in-hyperglycemia
#16
Danielle Desjardins, Yueying Liu, Craig E Crosson, Zsolt Ablonczy
In diabetic individuals, macular edema is a major cause of vision loss. This condition is refractory to insulin therapy and has been attributed to metabolic memory. The retinal pigment epithelium (RPE) is central to maintaining fluid balance in the retina, and this function is compromised by the activation of advanced glycation end-product receptors (RAGE). Here we provide evidence that acute administration of the RAGE agonist, glycated-albumin (gAlb) or vascular endothelial growth factor (VEGF), increased histone deacetylase (HDAC) activity in RPE cells...
2016: PloS One
https://www.readbyqxmd.com/read/27604094/regulation-of-platelet-function-by-acetylation-deacetylation-mechanisms
#17
REVIEW
Ana Latorre, Antonio Moscardó
Reversible acetylation of histones is a well-known mechanism of epigenetic regulation of gene expression. More recently, studies have demonstrated that acetylation/deacetylation in several proteins regulate multiple aspects of cellular activity, especially those associated with energetic metabolism. Platelets are key participants in haemostasis and cardiovascular diseases. Although metabolic changes such as diabetes or lipidemia are well recognized risk factors for cardiovascular diseases, there is very little information about the relationship between metabolism and platelet reactivity...
2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27556491/epigenetic-activation-of-wnt-%C3%AE-catenin-signaling-in-nafld-associated-hepatocarcinogenesis
#18
REVIEW
Yuan Tian, Myth T S Mok, Pengyuan Yang, Alfred S L Cheng
Non-alcoholic fatty liver disease (NAFLD), characterized by fat accumulation in liver, is closely associated with central obesity, over-nutrition and other features of metabolic syndrome, which elevate the risk of developing hepatocellular carcinoma (HCC). The Wnt/β-catenin signaling pathway plays a significant role in the physiology and pathology of liver. Up to half of HCC patients have activation of Wnt/β-catenin signaling. However, the mutation frequencies of CTNNB1 (encoding β-catenin protein) or other antagonists targeting Wnt/β-catenin signaling are low in HCC patients, suggesting that genetic mutations are not the major factor driving abnormal β-catenin activities in HCC...
2016: Cancers
https://www.readbyqxmd.com/read/27542279/conditional-ablation-of-hdac3-in-islet-beta-cells-results-in-glucose-intolerance-and-enhanced-susceptibility-to-stz-induced-diabetes
#19
Wen-Bin Chen, Ling Gao, Jie Wang, Yan-Gang Wang, Zheng Dong, Jiajun Zhao, Qing-Sheng Mi, Li Zhou
Histone deacetylases (HDACs) are enzymes that regulate gene expression by modifying chromatin structure through removal of acetyl groups from target histones or non-histone proteins. Previous in vitro studies suggest that HDACs may be novel pharmacological targets in immune-mediated islet β-cell destruction. However, the role of specific HDAC in islet β-cell development and function remain unclear. Here, we generated a conditional islet β-cells specific HDAC3 deletion mouse model to determine the consequences of HDAC3 depletion on islet β-cell differentiation, maintenance and function...
September 6, 2016: Oncotarget
https://www.readbyqxmd.com/read/27536685/sirt1-and-kidney-function
#20
REVIEW
Yi Guan, Chuan-Ming Hao
BACKGROUND: SIRT1 is a nicotinamide adenine dinucleotide-dependent deacetylase belonging to the class III histone deacetylases. Abundantly expressed in the kidney, especially in the renal medulla, SIRT1 is closely involved in renal physiology and pathology. SUMMARY: SIRT1 targets both histone and nonhistone proteins, participates in many important signaling pathways and mediates the regulation of longevity, metabolic homeostasis, acute stress response and DNA integrity...
March 2016: Kidney Diseases
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