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histone deacetylase insulin resistance

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https://www.readbyqxmd.com/read/29298809/sucrose-non-fermenting-related-kinase-regulates-both-adipose-inflammation-and-energy-homeostasis-in-mice-and-humans
#1
Jie Li, Bin Feng, Yaohui Nie, Ping Jiao, Xiaochen Lin, Mengna Huang, Ran An, Qin He, Huilin Emily Zhou, Arthur Salomon, Kirsten S Sigrist, Zhidan Wu, Simin Liu, Haiyan Xu
Sucrose non-fermenting related kinase (SNRK) is a member of AMPK-related kinase family and its physiological role in adipose energy homeostasis and inflammation remains unknown. We previously reported that SNRK is ubiquitously and abundantly expressed in both white (WAT) and brown adipose tissue (BAT) but adipose SNRK expression level diminishes in obesity. In the current study, we report novel experimental findings from both animal models and human genetics. SNRK is essential for survival since SNRK global deficient pups die within 24 hours after birth...
January 3, 2018: Diabetes
https://www.readbyqxmd.com/read/29211738/metformin-inhibits-the-development-and-promotes-the-resensitization-of-treatment-resistant-breast-cancer
#2
Gerald Davies, Liubov Lobanova, Wojciech Dawicki, Gary Groot, John R Gordon, Matthew Bowen, Troy Harkness, Terra Arnason
Multiple drug resistant (MDR) malignancy remains a predictable and often terminal event in cancer therapy, and affects individuals with many cancer types, regardless of the stage at which they were originally diagnosed or the interval from last treatment. Protein biomarkers of MDR are not globally used for clinical decision-making, but include the overexpression of drug-efflux pumps (ABC transporter family) such as MDR-1 and BCRP, as well as HIF1α, a stress responsive transcription factor found elevated within many MDR tumors...
2017: PloS One
https://www.readbyqxmd.com/read/29189132/polyphenols-novel-signaling-pathways
#3
Marie-Louise Ricketts, Bradley S Ferguson
BACKGROUND: Cardiovascular disease (CVD) is currently the leading cause of death globally. The metabolic syndrome (MetS), a clustering of risk factors including hypertension, hyperglycemia, elevated low-density lipoprotein (LDL) cholesterol, reduced high-density lipoprotein (HDL) cholesterol and increased visceral adiposity, is a significant risk factor for the development of CVD. Non-alcoholic fatty liver disease (NAFLD), often referred to as the hepatic manifestation of MetS, is a constellation of progressive liver disorders closely linked to obesity, diabetes, and insulin resistance...
November 29, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28757615/ror%C3%AE-controls-hepatic-lipid-homeostasis-via-negative-regulation-of-ppar%C3%AE-transcriptional-network
#4
Kyeongkyu Kim, Kyungjin Boo, Young Suk Yu, Se Kyu Oh, Hyunkyung Kim, Yoon Jeon, Jinhyuk Bhin, Daehee Hwang, Keun Il Kim, Jun-Su Lee, Seung-Soon Im, Seul Gi Yoon, Il Yong Kim, Je Kyung Seong, Ho Lee, Sungsoon Fang, Sung Hee Baek
The retinoic acid receptor-related orphan receptor-α (RORα) is an important regulator of various biological processes, including cerebellum development, circadian rhythm and cancer. Here, we show that hepatic RORα controls lipid homeostasis by negatively regulating transcriptional activity of peroxisome proliferators-activated receptor-γ (PPARγ) that mediates hepatic lipid metabolism. Liver-specific Rorα-deficient mice develop hepatic steatosis, obesity and insulin resistance when challenged with a high-fat diet (HFD)...
July 31, 2017: Nature Communications
https://www.readbyqxmd.com/read/28533215/inhibition-of-hdac3-prevents-diabetic-cardiomyopathy-in-ove26-mice-via-epigenetic-regulation-of-dusp5-erk1-2-pathway
#5
Zheng Xu, Qian Tong, Zhiguo Zhang, Shudong Wang, Yang Zheng, Qiuju Liu, Ling-Bo Qian, Shao-Yu Chen, Jian Sun, Lu Cai
Inhibition of total histone deacetylases (HDACs) was phenomenally associated with the prevention of diabetic cardiomyopathy (DCM). However, which specific HDAC plays the key role in DCM remains unclear. The present study was designed to determine whether DCM can be prevented by specific inhibition of HDAC3 and to elucidate the mechanisms by which inhibition of HDAC3 prevents DCM. Type 1 diabetes OVE26 and age-matched wild-type (WT) mice were given the selective HDAC3 inhibitor RGFP966 or vehicle for 3 months...
August 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28470097/phenylbutyrate-and-%C3%AE-cell-function-contribution-of-histone-deacetylases-and-er-stress-inhibition
#6
Sabbir Khan, Sandeep K Komarya, Gopabandhu Jena
Incidences of diabetes are increasing globally due to involvement of genetic and epigenetic factors. Phenylbutyrate (PBA) is a US FDA approved drug for treatment of urea cycle disorder in children. PBA reduces endoplasmic reticulum (ER) stress and is proven as a potent histone deacetylases (HDACs) inhibitor. Chronic ER stress results in unfolding protein response, which triggers apoptosis. Abnormal ER homoeostasis is responsible for defective processing of several genes/proteins and contributes to β-cell death/failure...
May 4, 2017: Epigenomics
https://www.readbyqxmd.com/read/28109123/sodium-butyrate-protects-against-high-fat-diet-induced-cardiac-dysfunction-and-metabolic-disorders-in-type-ii-diabetic-mice
#7
Ling Zhang, Jianfeng Du, Naohiro Yano, Hao Wang, Yu Tina Zhao, Patrycja M Dubielecka, Shougang Zhuang, Y Eugene 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...
August 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27991918/dissociation-of-muscle-insulin-sensitivity-from-exercise-endurance-in-mice-by-hdac3-depletion
#8
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...
February 2017: Nature Medicine
https://www.readbyqxmd.com/read/27988168/dna-methylation-and-histone-deacetylation-regulating-insulin-sensitivity-due-to-chronic-cold-exposure
#9
Xiaoqing Wang, Lai Wang, Yizheng Sun, Ruiping Li, Jinbo Deng, Jiexin Deng
In this study, we investigated the causal relationship between chronic cold exposure and insulin resistance and the mechanisms of how DNA methylation and histone deacetylation regulate cold-reduced insulin resistance. 46 adult male mice from postnatal day 90-180 were randomly assigned to control group and cold-exposure group. Mice in cold-exposure group were placed at temperature from -1 to 4 °C for 30 days to mimic chronic cold environment. Then, fasting blood glucose, blood insulin level and insulin resistance index were measured with enzymatic methods...
February 2017: Cryobiology
https://www.readbyqxmd.com/read/27906092/alterations-to-mtorc1-signaling-in-the-skeletal-muscle-differentially-affect-whole-body-metabolism
#10
Maitea Guridi, Barbara Kupr, Klaas Romanino, Shuo Lin, Denis Falcetta, Lionel Tintignac, Markus A Rüegg
BACKGROUND: The mammalian target of rapamycin complex 1 (mTORC1) is a central node in a network of signaling pathways controlling cell growth and survival. This multiprotein complex integrates external signals and affects different nutrient pathways in various organs. However, it is not clear how alterations of mTORC1 signaling in skeletal muscle affect whole-body metabolism. RESULTS: We characterized the metabolic phenotype of young and old raptor muscle knock-out (RAmKO) and TSC1 muscle knock-out (TSCmKO) mice, where mTORC1 activity in skeletal muscle is inhibited or constitutively activated, respectively...
March 21, 2016: Skeletal Muscle
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
#11
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/27877053/synergistic-activity-of-vorinostat-combined-with-gefitinib-but-not-with-sorafenib-in-mutant-kras-human-non-small-cell-lung-cancers-and-hepatocarcinoma
#12
Victor Jeannot, Benoit Busser, Laetitia Vanwonterghem, Sophie Michallet, Sana Ferroudj, Murat Cokol, Jean-Luc Coll, Mehmet Ozturk, Amandine Hurbin
Development of drug resistance limits the efficacy of targeted therapies. Alternative approaches using different combinations of therapeutic agents to inhibit several pathways could be a more effective strategy for treating cancer. The effects of the approved epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (gefitinib) or a multi-targeted kinase inhibitor (sorafenib) in combination with a histone deacetylase inhibitor (vorinostat) on cell proliferation, cell cycle distribution, apoptosis, and signaling pathway activation in human lung adenocarcinoma and hepatocarcinoma cells with wild-type EGFR and mutant KRAS were investigated...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27852975/rpd3-interacts-with-insulin-signaling-in-drosophila-longevity-extension
#13
Jared K Woods, Tahereh Ziafazeli, Blanka Rogina
Histone deacetylase (HDAC) 1 regulates chromatin compaction and gene expression by removing acetyl groups from lysine residues within histones. HDAC1 affects a variety of processes including proliferation, development, metabolism, and cancer. Reduction or inhibition of Rpd3, yeast and fly HDAC1 orthologue, extends longevity. However, the mechanism of rpd3's effects on longevity remains unclear. Here we report an overlap between rpd3 and the Insulin/Insulin-like growth factor signaling (IIS) longevity pathways...
November 14, 2016: Aging
https://www.readbyqxmd.com/read/27807598/salt-inducible-kinase-2-and-3-are-downregulated-in-adipose-tissue-from-obese-or-insulin-resistant-individuals-implications-for-insulin-signalling-and-glucose-uptake-in-human-adipocytes
#14
Johanna Säll, Annie M L Pettersson, Christel Björk, Emma Henriksson, Sebastian Wasserstrom, Wilhelm Linder, Yuedan Zhou, Ola Hansson, Daniel P Andersson, Mikael Ekelund, Eva Degerman, Karin G Stenkula, Jurga Laurencikiene, Olga Göransson
AIMS/HYPOTHESIS: Salt-inducible kinases (SIKs) are related to the metabolic regulator AMP-activated protein kinase (AMPK). SIK2 is abundant in adipose tissue. The aims of this study were to investigate the expression of SIKs in relation to human obesity and insulin resistance, and to evaluate whether changes in the expression of SIKs might play a causal role in the development of disturbed glucose uptake in human adipocytes. METHODS: SIK mRNA and protein was determined in human adipose tissue or adipocytes, and correlated to clinical variables...
February 2017: Diabetologia
https://www.readbyqxmd.com/read/27634872/mitochondrial-aldehyde-dehydrogenase-obliterates-insulin-resistance-induced-cardiac-dysfunction-through-deacetylation-of-pgc-1%C3%AE
#15
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...
November 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/27620069/histone-deacetylase-inhibitors-future-therapeutics-for-insulin-resistance-and-type-2-diabetes
#16
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/27619406/the-histone-deacetylase-inhibitor-sodium-butyrate-improves-insulin-signalling-in-palmitate-induced-insulin-resistance-in-l6-rat-muscle-cells-through-epigenetically-mediated-up-regulation-of-irs1
#17
Sabrina Chriett, Ouafa Zerzaihi, Hubert Vidal, Luciano Pirola
Dietary administration of the histone deacetylase (HDAC) inhibitor butyric acid - a short chain fatty acid present in milk products and also bacterially produced in the intestine - has been shown to increase energy expenditure and favour insulin sensitivity in mice through induction of PGC1α (peroxisome proliferator-activated receptor gamma co-activator 1α) and AMPK (AMP-activated protein kinase) in skeletal muscle, and a consequential increase of mitochondrial fatty acid oxidation. Here, we investigate whether such physiological improvements are associated to epigenetic effects dependent on increased histone acetylation and whether butyrate exerts a direct action on skeletal muscle insulin signalling...
September 13, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27617745/histone-deacetylase-inhibition-restores-retinal-pigment-epithelium-function-in-hyperglycemia
#18
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/27582487/essential-role-of-dna-methyltransferase-1-mediated-transcription-of-insulin-like-growth-factor-2-in-resistance-to-histone-deacetylase-inhibitors
#19
Hye-Young Min, Su-Chan Lee, Jong Kyu Woo, Hyun Jin Jung, Kwan Hee Park, Hae Min Jeong, Seung Yeob Hyun, Jaebeom Cho, Wooin Lee, Ji Eun Park, So Jung Kwon, Hyo-Jong Lee, Xiao Ni, Young Kee Shin, Faye M Johnson, Madeleine Duvic, Ho-Young Lee
Purpose: Histone deacetylase inhibitors (HDI) are promising anticancer therapies; however, drug resistance limits their efficacy. Here, we investigated the molecular mechanisms underlying HDI resistance, focusing on the mechanism of HDI-mediated induction of insulin-like growth factor 2 (IGF2) based on our previous study.Experimental Design: The methylation status of CCCTC-binding factor (CTCF)-binding sites in the IGF2/H19 imprinting control region (ICR) were determined by methylation-specific PCR and bisulfite sequencing...
March 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27528227/butyrate-alleviates-high-fat-diet-induced-obesity-through-activation-of-adiponectin-mediated-pathway-and-stimulation-of-mitochondrial-function-in-the-skeletal-muscle-of-mice
#20
Jian Hong, Yimin Jia, Shifeng Pan, Longfei Jia, Huifang Li, Zhenqiang Han, Demin Cai, Ruqian Zhao
Dietary supplementation of butyrate can prevent diet-induced obesity through increasing mitochondrial function in mice, yet the up-stream signaling pathway remains elusive. In this study, weaned mice were divided into two groups, fed control (CON) and high-fat diet (HF, 45% energy from fat), respectively, for 8 weeks. HF-induced obese mice, maintained on HF diet, were then divided into two groups; HFB group was gavaged with 80 mg sodium butyrate (SB) per mice every other day for 10 days, while the HF group received vehicle...
August 30, 2016: Oncotarget
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