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histone deacetylase insulin resistance

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https://www.readbyqxmd.com/read/27906092/alterations-to-mtorc1-signaling-in-the-skeletal-muscle-differentially-affect-whole-body-metabolism
#1
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
#2
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
#3
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
#4
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
#5
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...
November 2, 2016: Diabetologia
https://www.readbyqxmd.com/read/27634872/mitochondrial-aldehyde-dehydrogenase-obliterates-insulin-resistance-induced-cardiac-dysfunction-through-deacetylation-of-pgc-1%C3%AE
#6
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/27620069/histone-deacetylase-inhibitors-future-therapeutics-for-insulin-resistance-and-type-2-diabetes
#7
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
#8
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
#9
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
#10
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 (HDIs) 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...
August 31, 2016: 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
#11
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 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27479696/acetylation-control-of-cardiac-fatty-acid-%C3%AE-oxidation-and-energy-metabolism-in-obesity-diabetes-and-heart-failure
#12
Arata Fukushima, Gary D Lopaschuk
Alterations in cardiac energy metabolism are an important contributor to the cardiac pathology associated with obesity, diabetes, and heart failure. High rates of fatty acid β-oxidation with cardiac insulin resistance represent a cardiac metabolic hallmark of diabetes and obesity, while a marginal decrease in fatty acid oxidation and a prominent decrease in insulin-stimulated glucose oxidation are commonly seen in the early stages of heart failure. Alterations in post-translational control of energy metabolic processes have recently been identified as an important contributor to these metabolic changes...
July 29, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27411688/epigenetic-mechanisms-of-cell-adhesion-mediated-drug-resistance-in-multiple-myeloma
#13
REVIEW
Yusuke Furukawa, Jiro Kikuchi
Multiple myeloma cells acquire the resistance to anti-cancer drugs through physical and functional interactions with the bone marrow microenvironment via two overlapping mechanisms. First, bone marrow stromal cells (BMSCs) produce soluble factors, such as interleukin-6 and insulin-like growth factor-1, to activate signal transduction pathways leading to drug resistance (soluble factor-mediated drug resistance). Second, BMSCs up-regulate the expression of cell cycle inhibitors, anti-apoptotic members of the Bcl-2 family and ABC drug transporters in myeloma cells upon direct adhesion [cell adhesion-mediated drug resistance (CAM-DR)]...
September 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27270450/sodium-butyrate-reduces-insulin-resistance-fat-accumulation-and-dyslipidemia-in-type-2-diabetic-rat-a-comparative-study-with-metformin
#14
Sabbir Khan, Gopabandhu Jena
Recent evidences highlighted that histone deacetylases (HDACs) can deacetylate the histone, various transcription factors and regulatory proteins, which directly or indirectly affect glucose metabolism. The present study aimed to evaluate the comparative effects of sodium butyrate (NaB) and metformin on the glucose homeostasis, insulin-resistance, fat accumulation and dyslipidemia in type-2 diabetic rat. Diabetes was developed in Sprague-Dawley rats by the combination of high-fat diet (HFD) and low dose streptozotocin (STZ, 35 mg/kg)...
July 25, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/27239042/hepatocyte-dach1-is-increased-in-obesity-via-nuclear-exclusion-of-hdac4-and-promotes-hepatic-insulin-resistance
#15
Lale Ozcan, Devram S Ghorpade, Ze Zheng, Jane Cristina de Souza, Ke Chen, Marc Bessler, Melissa Bagloo, Beth Schrope, Richard Pestell, Ira Tabas
Defective insulin signaling in hepatocytes is a key factor in type 2 diabetes. In obesity, activation of calcium/calmodulin-dependent protein kinase II (CaMKII) in hepatocytes suppresses ATF6, which triggers a PERK-ATF4-TRB3 pathway that disrupts insulin signaling. Elucidating how CaMKII suppresses ATF6 is therefore essential to understanding this insulin resistance pathway. We show that CaMKII phosphorylates and blocks nuclear translocation of histone deacetylase 4 (HDAC4). As a result, HDAC4-mediated SUMOylation of the corepressor DACH1 is decreased, which protects DACH1 from proteasomal degradation...
June 7, 2016: Cell Reports
https://www.readbyqxmd.com/read/27086926/essential-role-of-insulin-like-growth-factor-2-in-resistance-to-histone-deacetylase-inhibitors
#16
S-C Lee, H-Y Min, H J Jung, K H Park, S Y Hyun, J Cho, J K Woo, S J Kwon, H-J Lee, F M Johnson, H-Y Lee
Histone deacetylase (HDAC) inhibitors (HDIs) are promising anticancer therapies and have been clinically used for the treatment of hematological malignancy. However, their efficacy in solid tumors is marginal and drug resistance hampers their further clinical utility. To develop novel strategies for the HDI-based anticancer therapeutics in non-small cell lung cancer (NSCLC), in the present study, we investigated the mechanisms underlying resistance to HDI treatment in NSCLC cells. We show the STAT3-mediated IGF2/IGF-1R signaling cascade as a key modulator for both acquired and primary HDI resistance...
April 18, 2016: Oncogene
https://www.readbyqxmd.com/read/27004103/alterations-to-mtorc1-signaling-in-the-skeletal-muscle-differentially-affect-whole-body-metabolism
#17
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...
2016: Skeletal Muscle
https://www.readbyqxmd.com/read/26944797/valproic-acid-reduces-insulin-resistance-fat-deposition-and-foxo1-mediated-gluconeogenesis-in-type-2-diabetic-rat
#18
Sabbir Khan, Sandeep Kumar, Gopabandhu Jena
Recent evidences highlighted the role of histone deacetylases (HDACs) in insulin-resistance, gluconeogenesis and islet function. HDACs can modulate the expression of various genes, which directly or indirectly affect glucose metabolism. This study was aimed to evaluate the role of valproic acid (VPA) on fat deposition, insulin-resistance and gluconeogenesis in type-2 diabetic rat. Diabetes was developed in Sprague-Dawley rats by the combination of high-fat diet and low dose streptozotocin. VPA at the doses of 150 and 300 mg/kg/day and metformin (positive control) 150 mg/kg twice daily for 10 weeks were administered by oral gavage...
June 2016: Biochimie
https://www.readbyqxmd.com/read/26805421/epigenetic-modifications-by-inhibiting-histone-deacetylases-reverse-memory-impairment-in-insulin-resistance-induced-cognitive-deficit-in-mice
#19
Sorabh Sharma, Rajeev Taliyan
Insulin resistance has been reported as a strong risk factor for Alzheimer's disease. However the molecular mechanisms of association between these still remain elusive. Various studies have highlighted the involvement of histone deacetylases (HDACs) in insulin resistance and cognitive deficits. Thus, the present study was designed to investigate the possible neuroprotective role of HDAC inhibitor, suberoylanilide hydroxamic acid (SAHA) in insulin resistance induced cognitive impairment in mice. Mice were subjected to either normal pellet diet (NPD) or high fat diet (HFD) for 8 weeks...
June 2016: Neuropharmacology
https://www.readbyqxmd.com/read/26453063/glucose-induced-expression-of-the-homeotic-transcription-factor-prep1-is-associated-with-histone-post-translational-modifications-in-skeletal-muscle
#20
Marco Ciccarelli, Viviana Vastolo, Luigi Albano, Manuela Lecce, Serena Cabaro, Antonietta Liotti, Michele Longo, Francesco Oriente, Gian Luigi Russo, Paolo Emidio Macchia, Pietro Formisano, Francesco Beguinot, Paola Ungaro
AIMS/HYPOTHESIS: Chronic hyperglycaemia worsens insulin resistance in individuals with type 2 diabetes. Whether this effect is contributed by epigenetic dysregulation and which genes are involved remain unclear. Prep1 (also known as Pknox1) is a gene exerting major effects on the sensitivity of the glucose transport machinery to insulin. Here, we show that dysregulation of Prep1 expression by high glucose levels is associated with histone modifications at its 5' regulatory region. METHODS: We used mouse and cell models to investigate Prep1 transcriptional regulation by glucose...
January 2016: Diabetologia
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