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Review

Personalized Epigenetic Management of Diabetes

, &
Pages 531-549 | Received 09 Jun 2017, Accepted 31 Aug 2017, Published online: 24 Nov 2017

References

  • International Diabetes Federation . IDF Diabetes Atlas (7th edition) ( 2015 ). www.diabetesatlas.org .
  • Fodor A , CozmaA , KarnieliE . Personalized epigenetic management of diabetes . Per. Med.12 ( 5 ), 497 – 514 ( 2015 ).
  • Van Kruijsbergen I , HontelezS , VeenstraGJ . Recruiting polycomb to chromatin . Int. J. Biochem. Cell Biol.67 , 177 – 187 ( 2015 ).
  • Lenoir O , FlosseauK , MaFX Specific control of pancreatic endocrine beta- and delta-cell mass by class IIa histone deacetylases HDAC4, HDAC5, and HDAC9 . Diabetes60 ( 11 ), 2861 – 2871 ( 2011 ).
  • Dhawan S , GeorgiaS , TschenSI , FanG , BhushanA . Pancreatic beta-cell identity is maintained by DNA methylation-mediated repression of Arx . Dev. Cell20 ( 4 ), 419 – 429 ( 2011 ).
  • Andrali SS , SampleyML , VanderfordNL , OzcanS . Glucose regulation of insulin gene expression in pancreatic beta-cells . Biochem. J.415 ( 1 ), 1 – 10 ( 2008 ).
  • Deering TG , OgiharaT , TraceAP , MaierB , MirmiraRG . Methyltransferase Set7/9 maintains transcription and euchromatin structure at islet-enriched genes . Diabetes58 ( 1 ), 185 – 193 ( 2009 ).
  • Maganti AV , MaierB , TerseySA Transcriptional activity of the islet beta cell factor Pdx1 is augmented by lysine methylation catalyzed by the methyltransferase Set7/9 . J. Biol. Chem.290 ( 15 ), 9812 – 9822 ( 2015 ).
  • Bernstein DL , Le LayJE , RuanoEG , KaestnerKH . TALE-mediated epigenetic suppression of CDKN2A increases replication in human fibroblasts . J. Clin. Invest.125 ( 5 ), 1998 – 2006 ( 2015 ).
  • El Ouaamari A , BaroukhN , MartensGA , LebrunP , PipeleersD , Van ObberghenE . miR-375 targets 3′-phosphoinositide-dependent protein kinase-1 and regulates glucose-induced biological responses in pancreatic beta-cells . Diabetes57 ( 10 ), 2708 – 2717 ( 2008 ).
  • Ramachandran D , RoyU , GargS , GhoshS , PathakS , Kolthur-SeetharamU . Sirt1 and mir-9 expression is regulated during glucose-stimulated insulin secretion in pancreatic beta-islets . FEBS J.278 ( 7 ), 1167 – 1174 ( 2011 ).
  • Melkman-Zehavi T , OrenR , Kredo-RussoS miRNAs control insulin content in pancreatic beta-cells via downregulation of transcriptional repressors . EMBO J.30 ( 5 ), 835 – 845 ( 2011 ).
  • Akerman I , TuZ , BeucherA Human pancreatic beta cell lncRNAs control cell-specific regulatory networks . Cell Metab.25 ( 2 ), 400 – 411 ( 2017 ).
  • Lam HV , NguyenDT , NguyenCD . Sibling method increases risk assessment estimates for Type 1 diabetes . PLoS ONE12 ( 5 ), e0176341 ( 2017 ).
  • Li Y , ZhaoM , HouC Abnormal DNA methylation in CD4+ T cells from people with latent autoimmune diabetes in adults . Diabetes Res. Clin. Pract.94 ( 2 ), 242 – 248 ( 2011 ).
  • Miao F , SmithDD , ZhangL , MinA , FengW , NatarajanR . Lymphocytes from patients with Type 1 diabetes display a distinct profile of chromatin histone H3 lysine 9 dimethylation: an epigenetic study in diabetes . Diabetes57 ( 12 ), 3189 – 3198 ( 2008 ).
  • Liu XY , XuJF . Reduced histone H3 acetylation in CD4(+) T Lymphocytes: potential mechanism of latent autoimmune diabetes in adults . Dis. Markers 2015 , 285125 ( 2015 ).
  • Lawrence MC , ShaoC , McglynnK , NaziruddinB , LevyMF , CobbMH . Multiple chromatin-bound protein kinases assemble factors that regulate insulin gene transcription . Proc. Natl Acad. Sci. USA106 ( 52 ), 22181 – 22186 ( 2009 ).
  • Miao F , ChenZ , GenuthS Evaluating the role of epigenetic histone modifications in the metabolic memory of Type 1 diabetes . Diabetes63 ( 5 ), 1748 – 1762 ( 2014 ).
  • Fuchsberger C , FlannickJ , TeslovichTM The genetic architecture of Type 2 diabetes . Nature536 ( 7614 ), 41 – 47 ( 2016 ).
  • Heijmans BT , TobiEW , SteinAD Persistent epigenetic differences associated with prenatal exposure to famine in humans . Proc. Natl Acad. Sci. USA105 ( 44 ), 17046 – 17049 ( 2008 ).
  • Masuyama H , MitsuiT , NobumotoE , HiramatsuY . The effects of high-fat diet exposure in utero on the obesogenic and diabetogenic traits through epigenetic changes in adiponectin and leptin gene expression for multiple generations in female mice . Endocrinology156 ( 7 ), 2482 – 2491 ( 2015 ).
  • Dabelea D , HansonRL , LindsayRS Intrauterine exposure to diabetes conveys risks for Type 2 diabetes and obesity: a study of discordant sibships . Diabetes49 ( 12 ), 2208 – 2211 ( 2000 ).
  • Chen ACH , LeeYL , FongSW , WongCCY , NgEHY , YeungWSB . Hyperglycemia impedes definitive endoderm differentiation of human embryonic stem cells by modulating histone methylation patterns . Cell Tissue Res.368 ( 3 ), 563 – 578 ( 2017 ).
  • Chen P , PiaggiP , TraurigM Differential methylation of genes in individuals exposed to maternal diabetes in utero . Diabetologia60 ( 4 ), 645 – 655 ( 2017 ).
  • Donohoe DR , BultmanSJ . Metaboloepigenetics: interrelationships between energy metabolism and epigenetic control of gene expression . J. Cell. Physiol.227 ( 9 ), 3169 – 3177 ( 2012 ).
  • Chang HD , WangW , XiaW Epigenetic disruption and glucose homeostasis changes following low-dose maternal bisphenol A exposure . Tox. Res.5 , 1400 – 1409 ( 2016 ).
  • Lindholm ME , MarabitaF , Gomez-CabreroD An integrative analysis reveals coordinated reprogramming of the epigenome and the transcriptome in human skeletal muscle after training . Epigenetics9 ( 12 ), 1557 – 1569 ( 2014 ).
  • Ronn T , VolkovP , DavegardhC A six months exercise intervention influences the genome-wide DNA methylation pattern in human adipose tissue . PLoS Genet.9 ( 6 ), e1003572 ( 2013 ).
  • Ling C , Del GuerraS , LupiR Epigenetic regulation of PPARGC1A in human Type 2 diabetic islets and effect on insulin secretion . Diabetologia51 ( 4 ), 615 – 622 ( 2008 ).
  • Yang BT , DayehTA , KirkpatrickCL Insulin promoter DNA methylation correlates negatively with insulin gene expression and positively with HbA(1c) levels in human pancreatic islets . Diabetologia54 ( 2 ), 360 – 367 ( 2011 ).
  • Yang BT , DayehTA , VolkovPA Increased DNA methylation and decreased expression of PDX-1 in pancreatic islets from patients with Type 2 diabetes . Mol. Endocrinol.26 ( 7 ), 1203 – 1212 ( 2012 ).
  • Hall E , DayehT , KirkpatrickCL , WollheimCB , Dekker NitertM , LingC . DNA methylation of the glucagon-like peptide 1 receptor (GLP1R) in human pancreatic islets . BMC Med. Genet.14 , 76 ( 2013 ).
  • Dayeh T , VolkovP , SaloS Genome-wide DNA methylation analysis of human pancreatic islets from Type 2 diabetic and non-diabetic donors identifies candidate genes that influence insulin secretion . PLoS Genet.10 ( 3 ), e1004160 ( 2014 ).
  • Daneshpajooh M , BacosK , BysaniM HDAC7 is overexpressed in human diabetic islets and impairs insulin secretion in rat islets and clonal-cells . Diabetologia60 ( 1 ), 116 – 125 ( 2017 ).
  • Toperoff G , AranD , KarkJD Genome-wide survey reveals predisposing diabetes Type 2-related DNA methylation variations in human peripheral blood . Hum. Mol. Genet.21 ( 2 ), 371 – 383 ( 2012 ).
  • Luttmer R , SpijkermanAM , KokRM Metabolic syndrome components are associated with DNA hypomethylation . Obes. Res. Clin. Pract.7 ( 2 ), e106 – e115 ( 2013 ).
  • Pheiffer C , DiasS , MullerC , LouwJ . Decreased global DNA methylation in the white blood cells of high fat diet fed vervet monkeys (Chlorocebus aethiops) . J. Physiol. Biochem.70 ( 3 ), 725 – 733 ( 2014 ).
  • Canivell S , RuanoEG , Siso-AlmirallA Differential methylation of TCF7L2 promoter in peripheral blood DNA in newly diagnosed, drug-naive patients with Type 2 diabetes . PLoS ONE9 ( 6 ), e99310 ( 2014 ).
  • Miao F , GonzaloIG , LantingL , NatarajanR . In vivo chromatin remodeling events leading to inflammatory gene transcription under diabetic conditions . J. Biol. Chem.279 ( 17 ), 18091 – 18097 ( 2004 ).
  • Miao F , WuX , ZhangL , YuanYC , RiggsAD , NatarajanR . Genome-wide analysis of histone lysine methylation variations caused by diabetic conditions in human monocytes . J. Biol. Chem.282 ( 18 ), 13854 – 13863 ( 2007 ).
  • Li Y , ReddyMA , MiaoF Role of the histone H3 lysine 4 methyltransferase, SET7/9, in the regulation of NF-kappaB-dependent inflammatory genes. Relevance to diabetes and inflammation . J. Biol. Chem.283 ( 39 ), 26771 – 26781 ( 2008 ).
  • Brasacchio D , OkabeJ , TikellisC Hyperglycemia induces a dynamic cooperativity of histone methylase and demethylase enzymes associated with gene-activating epigenetic marks that coexist on the lysine tail . Diabetes58 ( 5 ), 1229 – 1236 ( 2009 ).
  • Chuang HC , WangJS , LeeIT , SheuWH , TanTH . Epigenetic regulation of HGK/MAP4K4 in T cells of Type 2 diabetes patients . Oncotarget7 ( 10 ), 10976 – 10989 ( 2016 ).
  • Sartorius T , StaigerH , KettererC Association of common genetic variants in the MAP4K4 locus with prediabetic traits in humans . PLoS ONE7 ( 10 ), e47647 ( 2012 ).
  • Zampetaki A , KiechlS , DrozdovI Plasma microRNA profiling reveals loss of endothelial miR-126 and other microRNAs in Type 2 diabetes . Circ. Res.107 ( 6 ), 810 – 817 ( 2010 ).
  • Li X , ZhaoZ , GaoC The diagnostic value of whole blood lncRNA ENST00000550337.1 for pre-diabetes and Type 2 diabetes mellitus . Exp. Clin. Endocrinol. Diabetes125 ( 6 ), 377 – 383 ( 2017 ).
  • Fujiki K , KanoF , ShiotaK , MurataM . Expression of the peroxisome proliferator activated receptor gamma gene is repressed by DNA methylation in visceral adipose tissue of mouse models of diabetes . BMC Biol.7 , 38 ( 2009 ).
  • Nilsson E , JanssonPA , PerfilyevA Altered DNA methylation and differential expression of genes influencing metabolism and inflammation in adipose tissue from subjects with Type 2 diabetes . Diabetes63 ( 9 ), 2962 – 2976 ( 2014 ).
  • Sakurai N , MochizukiK , GodaT . Modifications of histone H3 at lysine 9 on the adiponectin gene in 3T3-L1 adipocytes . J. Nutr. Sci. Vitaminol. (Tokyo)55 ( 2 ), 131 – 138 ( 2009 ).
  • Trajkovski M , HausserJ , SoutschekJ MicroRNAs 103 and 107 regulate insulin sensitivity . Nature474 ( 7353 ), 649 – 653 ( 2011 ).
  • Jordan SD , KrugerM , WillmesDM Obesity-induced overexpression of miRNA-143 inhibits insulin-stimulated AKT activation and impairs glucose metabolism . Nat. Cell Biol.13 ( 4 ), 434 – 446 ( 2011 ).
  • Zhou B , LiC , QiW Downregulation of miR-181a upregulates sirtuin-1 (SIRT1) and improves hepatic insulin sensitivity . Diabetologia55 ( 7 ), 2032 – 2043 ( 2012 ).
  • He A , ZhuL , GuptaN , ChangY , FangF . Overexpression of micro ribonucleic acid 29, highly up-regulated in diabetic rats, leads to insulin resistance in 3T3-L1 adipocytes . Mol. Endocrinol.21 ( 11 ), 2785 – 2794 ( 2007 ).
  • Kornfeld JW , BaitzelC , KonnerAC Obesity-induced overexpression of miR-802 impairs glucose metabolism through silencing of Hnf1b . Nature494 ( 7435 ), 111 – 115 ( 2013 ).
  • Shah R , MurthyV , PacoldM Extracellular RNAs are associated with insulin resistance and metabolic phenotypes . Diabetes Care40 ( 4 ), 546 – 553 ( 2017 ).
  • Sun L , GoffLA , TrapnellC Long noncoding RNAs regulate adipogenesis . Proc. Natl Acad. Sci. USA110 ( 9 ), 3387 – 3392 ( 2013 ).
  • Sun G , ReddyMA , YuanH , LantingL , KatoM , NatarajanR . Epigenetic histone methylation modulates fibrotic gene expression . J. Am. Soc. Nephrol.21 ( 12 ), 2069 – 2080 ( 2010 ).
  • Yuan H , ReddyMA , SunG Involvement of p300/CBP and epigenetic histone acetylation in TGF-beta1-mediated gene transcription in mesangial cells . Am. J. Physiol. Renal Physiol.304 ( 5 ), F601 – F613 ( 2013 ).
  • Chen J , GuoY , ZengW ER stress triggers MCP-1 expression through SET7/9-induced histone methylation in the kidneys of db/db mice . Am. J. Physiol. Renal Physiol.306 ( 8 ), F916 – F925 ( 2014 ).
  • Cai M , BompadaP , AtacD , LaaksoM , GroopL , De MarinisY . Epigenetic regulation of glucose-stimulated osteopontin (OPN) expression in diabetic kidney . Biochem. Biophys. Res. Commun.469 ( 1 ), 108 – 113 ( 2016 ).
  • De Marinis Y , CaiM , BompadaP Epigenetic regulation of the thioredoxin-interacting protein (TXNIP) gene by hyperglycemia in kidney . Kidney Int.89 ( 2 ), 342 – 353 ( 2016 ).
  • Reddy MA , SumanthP , LantingL Losartan reverses permissive epigenetic changes in renal glomeruli of diabetic db/db mice . Kidney Int.85 ( 2 ), 362 – 373 ( 2014 ).
  • Zhou X , ZangX , PonnusamyM Enhancer of zeste homolog 2 inhibition attenuates renal fibrosis by maintaining Smad7 and phosphatase and tensin homolog expression . J. Am. Soc. Nephrol.27 ( 7 ), 2092 – 2108 ( 2016 ).
  • Shah A , XiaL , MassonEA Thioredoxin-interacting protein deficiency protects against diabetic nephropathy . J. Am. Soc. Nephrol.26 ( 12 ), 2963 – 2977 ( 2015 ).
  • Chen Z , MiaoF , PatersonADet al. Epigenomic profiling reveals an association between persistence of DNA methylation and metabolic memory in the DCCT/EDIC Type 1 diabetes cohort . Proc. Natl Acad. Sci. USA113 ( 21 ), E3002 – E3011 ( 2016 ).
  • Ko YA , MohtatD , SuzukiM Cytosine methylation changes in enhancer regions of core pro-fibrotic genes characterize kidney fibrosis development . Genome Biol.14 ( 10 ), R108 ( 2013 ).
  • Hasegawa K , WakinoS , SimicP Renal tubular Sirt1 attenuates diabetic albuminuria by epigenetically suppressing Claudin-1 overexpression in podocytes . Nat. Med.19 ( 11 ), 1496 – 1504 ( 2013 ).
  • Marumo T , YagiS , KawarazakiW Diabetes induces aberrant DNA methylation in the proximal tubules of the kidney . J. Am. Soc. Nephrol.26 ( 10 ), 2388 – 2397 ( 2015 ).
  • Kato M , ArceL , WangM , PuttaS , LantingL , NatarajanR . A microRNA circuit mediates transforming growth factor-beta1 autoregulation in renal glomerular mesangial cells . Kidney Int.80 ( 4 ), 358 – 368 ( 2011 ).
  • Kato M , ZhangJ , WangM MicroRNA-192 in diabetic kidney glomeruli and its function in TGF-beta-induced collagen expression via inhibition of E-box repressors . Proc. Natl Acad. Sci. USA104 ( 9 ), 3432 – 3437 ( 2007 ).
  • Ho J , NgKH , RosenS , DostalA , GregoryRI , KreidbergJA . Podocyte-specific loss of functional microRNAs leads to rapid glomerular and tubular injury . J. Am. Soc. Nephrol.19 ( 11 ), 2069 – 2075 ( 2008 ).
  • Long J , WangY , WangW , ChangBH , DaneshFR . MicroRNA-29c is a signature microRNA under high glucose conditions that targets Sprouty homolog 1, and its in vivo knockdown prevents progression of diabetic nephropathy . J. Biol. Chem.286 ( 13 ), 11837 – 11848 ( 2011 ).
  • Krupa A , JenkinsR , LuoDD , LewisA , PhillipsA , FraserD . Loss of microRNA-192 promotes fibrogenesis in diabetic nephropathy . J. Am. Soc. Nephrol.21 ( 3 ), 438 – 447 ( 2010 ).
  • Delic D , EiseleC , SchmidRet al. Urinary exosomal miRNA signature in Type II diabetic nephropathy patients . PLoS ONE11 ( 3 ), e0150154 ( 2016 ).
  • Argyropoulos C , WangK , BernardoJ Urinary microRNA profiling predicts the development of microalbuminuria in patients with Type 1 diabetes . J. Clin. Med.4 ( 7 ), 1498 – 1517 ( 2015 ).
  • Gao Y , ChenZY , WangY , LiuY , MaJX , LiYK . Long non-coding RNA ASncmtRNA-2 is upregulated in diabetic kidneys and high glucose-treated mesangial cells . Exp. Ther. Med.13 ( 2 ), 581 – 587 ( 2017 ).
  • Zhong Q , KowluruRA . Epigenetic changes in mitochondrial superoxide dismutase in the retina and the development of diabetic retinopathy . Diabetes60 ( 4 ), 1304 – 1313 ( 2011 ).
  • Zhong Q , KowluruRA . Epigenetic modification of Sod2 in the development of diabetic retinopathy and in the metabolic memory: role of histone methylation . Invest. Ophthalmol. Vis. Sci.54 ( 1 ), 244 – 250 ( 2013 ).
  • Zhong Q , KowluruRA . Regulation of matrix metalloproteinase-9 by epigenetic modifications and the development of diabetic retinopathy . Diabetes62 ( 7 ), 2559 – 2568 ( 2013 ).
  • Kowluru RA , ShanY , MishraM . Dynamic DNA methylation of matrix metalloproteinase-9 in the development of diabetic retinopathy . Lab. Invest.96 ( 10 ), 1040 – 1049 ( 2016 ).
  • Kowluru RA , ShanY . Role of oxidative stress in epigenetic modification of MMP-9 promoter in the development of diabetic retinopathy . Graefes Arch. Clin. Exp. Ophthalmol.255 ( 5 ), 955 – 962 ( 2017 ).
  • Perrone L , DeviTS , HosoyaK , TerasakiT , SinghLP . Thioredoxin interacting protein (TXNIP) induces inflammation through chromatin modification in retinal capillary endothelial cells under diabetic conditions . J. Cell. Physiol.221 ( 1 ), 262 – 272 ( 2009 ).
  • Mishra M , ZhongQ , KowluruRA . Epigenetic modifications of Nrf2-mediated glutamate-cysteine ligase: implications for the development of diabetic retinopathy and the metabolic memory phenomenon associated with its continued progression . Free Radic. Biol. Med.75 , 129 – 139 ( 2014 ).
  • Mishra M , ZhongQ , KowluruRA . Epigenetic modifications of Keap1 regulate its interaction with the protective factor Nrf2 in the development of diabetic retinopathy . Invest. Ophthalmol. Vis. Sci.55 ( 11 ), 7256 – 7265 ( 2014 ).
  • Agardh E , LundstigA , PerfilyevA Genome-wide analysis of DNA methylation in subjects with Type 1 diabetes identifies epigenetic modifications associated with proliferative diabetic retinopathy . BMC Med.13 , 182 ( 2015 ).
  • Mortuza R , FengB , ChakrabartiS . miR-195 regulates SIRT1-mediated changes in diabetic retinopathy . Diabetologia57 ( 5 ), 1037 – 1046 ( 2014 ).
  • Kovacs B , LumayagS , CowanC , XuS . MicroRNAs in early diabetic retinopathy in streptozotocin-induced diabetic rats . Invest. Ophthalmol. Vis. Sci.52 ( 7 ), 4402 – 4409 ( 2011 ).
  • Murray AR , ChenQ , TakahashiY , ZhouKK , ParkK , MaJX . MicroRNA-200b downregulates oxidation resistance 1 (Oxr1) expression in the retina of Type 1 diabetes model . Invest. Ophthalmol. Vis. Sci.54 ( 3 ), 1689 – 1697 ( 2013 ).
  • Silva VA , PolesskayaA , SousaTA Expression and cellular localization of microRNA-29b and RAX, an activator of the RNA-dependent protein kinase (PKR), in the retina of streptozotocin-induced diabetic rats . Mol. Vis.17 , 2228 – 2240 ( 2011 ).
  • Feng B , ChenS , McarthurK miR-146a-mediated extracellular matrix protein production in chronic diabetes complications . Diabetes60 ( 11 ), 2975 – 2984 ( 2011 ).
  • Zhao S , LiT , LiJ miR-23b-3p induces the cellular metabolic memory of high glucose in diabetic retinopathy through a SIRT1-dependent signalling pathway . Diabetologia59 ( 3 ), 644 – 654 ( 2016 ).
  • Barutta F , BrunoG , MatulloG MicroRNA-126 and micro-/macrovascular complications of Type 1 diabetes in the EURODIAB Prospective Complications Study . Acta Diabetol.54 ( 2 ), 133 – 139 ( 2017 ).
  • Shan ZX , LinQX , DengCY miR-1/miR-206 regulate Hsp60 expression contributing to glucose-mediated apoptosis in cardiomyocytes . FEBS Lett.584 ( 16 ), 3592 – 3600 ( 2010 ).
  • Zhou CH , ZhangMX , ZhouSS SIRT1 attenuates neuropathic pain by epigenetic regulation of mGluR1/5 expressions in Type 2 diabetic rats . Pain158 ( 1 ), 130 – 139 ( 2017 ).
  • Zagni C , FlorestaG , MonciinoG , RescifinaA . The search for potent, small-molecule HDACIs in cancer treatment: a decade after vorinostat . Med. Res. Rev.37 ( 6 ), 1373 – 1428 ( 2017 ).
  • Larsen L , TonnesenM , RonnSG Inhibition of histone deacetylases prevents cytokine-induced toxicity in beta cells . Diabetologia50 ( 4 ), 779 – 789 ( 2007 ).
  • Lewis EC , BlaabjergL , StorlingJ The oral histone deacetylase inhibitor ITF2357 reduces cytokines and protects islet beta cells in vivo and in vitro . Mol. Med.17 ( 5–6 ), 369 – 377 ( 2011 ).
  • Susick L , SenanayakeT , VeluthakalR , WosterPM , KowluruA . A novel histone deacetylase inhibitor prevents IL-1beta induced metabolic dysfunction in pancreatic beta-cells . J. Cell. Mol. Med.13 ( 8B ), 1877 – 1885 ( 2009 ).
  • Chou DH , HolsonEB , WagnerFF Inhibition of histone deacetylase 3 protects beta cells from cytokine-induced apoptosis . Chem. Biol.19 ( 6 ), 669 – 673 ( 2012 ).
  • Raichur S , TehSH , OhwakiK Histone deacetylase 5 regulates glucose uptake and insulin action in muscle cells . J. Mol. Endocrinol.49 ( 3 ), 203 – 211 ( 2012 ).
  • Galmozzi A , MitroN , FerrariA Inhibition of class I histone deacetylases unveils a mitochondrial signature and enhances oxidative metabolism in skeletal muscle and adipose tissue . Diabetes62 ( 3 ), 732 – 742 ( 2013 ).
  • Yoshikawa M , HishikawaK , MarumoT , FujitaT . Inhibition of histone deacetylase activity suppresses epithelial-to-mesenchymal transition induced by TGF-beta1 in human renal epithelial cells . J. Am. Soc. Nephrol.18 ( 1 ), 58 – 65 ( 2007 ).
  • Advani A , HuangQ , ThaiK Long-term administration of the histone deacetylase inhibitor vorinostat attenuates renal injury in experimental diabetes through an endothelial nitric oxide synthase-dependent mechanism . Am. J. Pathol.178 ( 5 ), 2205 – 2214 ( 2011 ).
  • Gilbert RE , HuangQ , ThaiK Histone deacetylase inhibition attenuates diabetes-associated kidney growth: potential role for epigenetic modification of the epidermal growth factor receptor . Kidney Int.79 ( 12 ), 1312 – 1321 ( 2011 ).
  • Crosson CE , ManiSK , HusainS , AlsarrafO , MenickDR . Inhibition of histone deacetylase protects the retina from ischemic injury . Invest. Ophthalmol. Vis. Sci.51 ( 7 ), 3639 – 3645 ( 2010 ).
  • Kadiyala CS , ZhengL , DuY Acetylation of retinal histones in diabetes increases inflammatory proteins: effects of minocycline and manipulation of histone acetyltransferase (HAT) and histone deacetylase (HDAC) . J. Biol. Chem.287 ( 31 ), 25869 – 25880 ( 2012 ).
  • Thatava T , MaB , RohdeM , MayerH . Chromatin-remodeling factors allow differentiation of bone marrow cells into insulin-producing cells . Stem Cells24 ( 12 ), 2858 – 2867 ( 2006 ).
  • Jiang J , AuM , LuK Generation of insulin-producing islet-like clusters from human embryonic stem cells . Stem Cells25 ( 8 ), 1940 – 1953 ( 2007 ).
  • Katz LS , Geras-RaakaE , GershengornMC . Reprogramming adult human dermal fibroblasts to islet-like cells by epigenetic modification coupled to transcription factor modulation . Stem Cells Dev.22 ( 18 ), 2551 – 2560 ( 2013 ).
  • Vecellio M , SpallottaF , NanniS The histone acetylase activator pentadecylidenemalonate 1b rescues proliferation and differentiation in the human cardiac mesenchymal cells of Type 2 diabetic patients . Diabetes63 ( 6 ), 2132 – 2147 ( 2014 ).
  • Khor TO , HuangY , WuTY , ShuL , LeeJ , KongAN . Pharmacodynamics of curcumin as DNA hypomethylation agent in restoring the expression of Nrf2 via promoter CpGs demethylation . Biochem. Pharmacol.82 ( 9 ), 1073 – 1078 ( 2011 ).
  • Zhang C , SuZY , KhorTO , ShuL , KongAN . Sulforaphane enhances Nrf2 expression in prostate cancer TRAMP C1 cells through epigenetic regulation . Biochem. Pharmacol.85 ( 9 ), 1398 – 1404 ( 2013 ).
  • Lefebvre B , BelaichS , LongueJ 5′-AZA induces Ngn3 expression and endocrine differentiation in the PANC-1 human ductal cell line . Biochem. Biophys. Res. Commun.391 ( 1 ), 305 – 309 ( 2010 ).
  • Yuan Y , HartlandK , BoskovicZ A small-molecule inducer of PDX1 expression identified by high-throughput screening . Chem. Biol.20 ( 12 ), 1513 – 1522 ( 2013 ).
  • Shen W , TremblayMS , DeshmukhVA Small-molecule inducer of beta cell proliferation identified by high-throughput screening . J. Am. Chem. Soc.135 ( 5 ), 1669 – 1672 ( 2013 ).
  • Ostrom M , LofflerKA , EdfalkS Retinoic acid promotes the generation of pancreatic endocrine progenitor cells and their further differentiation into beta-cells . PLoS ONE3 ( 7 ), e2841 ( 2008 ).
  • Chen S , BorowiakM , FoxJL A small molecule that directs differentiation of human ESCs into the pancreatic lineage . Nat. Chem. Biol.5 ( 4 ), 258 – 265 ( 2009 ).
  • Kondo Y , ToyodaT , ItoR Identification of a small molecule that facilitates the differentiation of human iPSCs/ESCs and mouse embryonic pancreatic explants into pancreatic endocrine cells . Diabetologia60 ( 8 ), 1454 – 1466 ( 2017 ).
  • Wedeken L , LuoA , TremblayJR Adult murine pancreatic progenitors require epidermal growth factor and nicotinamide for self-renewal and differentiation in a serum- and conditioned medium-free culture . Stem Cells Dev.26 ( 8 ), 599 – 607 ( 2017 ).
  • Song MY , KimEK , MoonWS Sulforaphane protects against cytokine- and streptozotocin-induced beta-cell damage by suppressing the NF-kappaB pathway . Toxicol. Appl. Pharmacol.235 ( 1 ), 57 – 67 ( 2009 ).
  • Aggarwal BB . Targeting inflammation-induced obesity and metabolic diseases by curcumin and other nutraceuticals . Annu. Rev. Nutr.30 , 173 – 199 ( 2010 ).
  • Szkudelski T , SzkudelskaK . Anti-diabetic effects of resveratrol . Ann. NY Acad. Sci.1215 , 34 – 39 ( 2011 ).
  • Manna P , AchariAE , JainSK . Vitamin D supplementation inhibits oxidative stress and upregulate SIRT1/AMPK/GLUT4 cascade in high glucose-treated 3T3L1 adipocytes and in adipose tissue of high fat diet-fed diabetic mice . Arch. Biochem. Biophys.615 , 22 – 34 ( 2017 ).
  • Martin-Nunez GM , Cabrera-MuleroR , Rubio-MartinE Methylation levels of the SCD1 gene promoter and LINE-1 repeat region are associated with weight change: an intervention study . Mol. Nutr. Food Res.58 ( 7 ), 1528 – 1536 ( 2014 ).
  • Choi SE , FuT , SeokS Elevated microRNA-34a in obesity reduces NAD+ levels and SIRT1 activity by directly targeting NAMPT . Aging Cell12 ( 6 ), 1062 – 1072 ( 2013 ).
  • Kurtz CL , FanninEE , TothCL , PearsonDS , VickersKC , SethupathyP . Inhibition of miR-29 has a significant lipid-lowering benefit through suppression of lipogenic programs in liver . Sci. Rep.5 , 12911 ( 2015 ).
  • Mcarthur K , FengB , WuY , ChenS , ChakrabartiS . MicroRNA-200b regulates vascular endothelial growth factor-mediated alterations in diabetic retinopathy . Diabetes60 ( 4 ), 1314 – 1323 ( 2011 ).
  • Tewari S , ZhongQ , SantosJM , KowluruRA . Mitochondria DNA replication and DNA methylation in the metabolic memory associated with continued progression of diabetic retinopathy . Invest. Ophthalmol. Vis. Sci.53 ( 8 ), 4881 – 4888 ( 2012 ).
  • Bae JB . Perspectives of international human epigenome consortium . Genomics Inform11 ( 1 ), 7 – 14 ( 2013 ).
  • Chen S , FengB , GeorgeB , ChakrabartiR , ChenM , ChakrabartiS . Transcriptional coactivator p300 regulates glucose-induced gene expression in endothelial cells . Am. J. Physiol. Endocrinol. Metab.298 ( 1 ), E127 – E137 ( 2010 ).

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