Clinical relevance of epigenetics in the onset and management of type 2 diabetes mellitus

Epigenetics

Volumn 12, Issue 6, 2017, Pages 401-415

  Sommese, Linda ^a   Zullo, Alberto ^b,c   Mancini, Francesco Paolo ^b   Fabbricini, Rossella ^a   Soricelli, Andrea ^d,e   Napoli, Claudio ^a,d  

^a SECOND UNIVERSITY OF NAPLES   (Italy)

^b UNIVERSITY OF SANNIO   (Italy)

^c CEINGE BIOTECNOLOGIE AVANZATE   (Italy)

^d IRCCS SDN   (Italy)

^e UNIVERSITY OF NAPLES PARTHENOPE   (Italy)

Author keywords

Bioinformatics; epigenetics; inflammation; transgenerational epigenetics; translational medicine; type 2 diabetes

Indexed keywords

3 [4 [3 (3 FLUOROPHENYL) 3 OXO 1 PROPENYL] 1 METHYL 1H PYRROL 2 YL]ACRYLOHYDROXAMIC ACID; DNA METHYLTRANSFERASE 3A; DNA METHYLTRANSFERASE 3B; GIVINOSTAT; HISTONE ACETYLTRANSFERASE; HISTONE DEACETYLASE INHIBITOR; INTERLEUKIN 1; INTERLEUKIN 6; LONG UNTRANSLATED RNA; MICRORNA; N [2 [3 (1 PIPERAZINYLMETHYL)IMIDAZO[2,1 B]THIAZOL 6 YL]PHENYL] 2 QUINOXALINECARBOXAMIDE; PROTEIN INHIBITOR; RANTES; S ADENOSYLMETHIONINE; TOLL LIKE RECEPTOR 2; TRANSCRIPTION FACTOR FKHR; TUMOR NECROSIS FACTOR; VASCULAR CELL ADHESION MOLECULE 1; VITAMIN D; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; OSTEOPONTIN; TOLL LIKE RECEPTOR;

3' UNTRANSLATED REGION; BIOINFORMATICS; CELL DIFFERENTIATION; CELL REGENERATION; DNA METHYLATION; ENHANCER REGION; EPIGENETICS; GENE EXPRESSION; GENE EXPRESSION PROFILING; GENE OVEREXPRESSION; HISTONE MODIFICATION; HUMAN; IMMUNITY; INSULIN RESISTANCE; MASS SPECTROMETRY; METABOLIC DISORDER; MICROARRAY ANALYSIS; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PANCREAS ISLET BETA CELL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; BIOLOGICAL THERAPY; DIABETES MELLITUS, TYPE 2; GENETIC EPIGENESIS; GENETICS; INFLAMMATION; METABOLISM; PATHOLOGY; TRANSLATIONAL RESEARCH;

CELL- AND TISSUE-BASED THERAPY; DIABETES MELLITUS, TYPE 2; EPIGENESIS, GENETIC; HUMANS; INFLAMMATION; INSULIN RESISTANCE; INSULIN-SECRETING CELLS; NF-KAPPA B; OSTEOPONTIN; TOLL-LIKE RECEPTORS; TRANSLATIONAL MEDICAL RESEARCH;

EID: 85020478301     PISSN: 15592294     EISSN: 15592308     Source Type: Journal    
DOI: 10.1080/15592294.2016.1278097     Document Type: Review

References (115)

1. American Diabetes Association. Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2008; 31:S55-60; PMID:18165338; https://doi.org/10.2337/dc08-S055
2. Gray SP, Jandeleit-Dahm K. The pathobiology of diabetic vascular complications cardiovascular and kidney disease. J Mol Med (Berl) 2014; 92:441-52; PMID:24687627; https://doi.org/10.1007/s00109-014-1146-1
3. Picascia A, Grimaldi V, Iannone C, Soricelli A, Napoli C. Innate and adaptive immune response in stroke:Focus on epigenetic regulation. J Neuroimmunol 2015; 289:111-20; PMID:26616880; https://doi.org/10.1016/j.jneuroim.2015.10.013
4. Prentki M, Nolan CJ. Islet beta cell failure in type 2 diabetes. J Clin Invest 2006; 116:1802-12; PMID:16823478; https://doi.org/10.1172/JCI29103
5. Donath MY, Shoelson SE. Type 2 diabetes as an inflammatory disease. Nat Rev Immunol 2011; 11:98-107; PMID:21233852; https://doi.org/10.1038/nri2925
6. Guariguata L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U, Shaw JE. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract 2014; 103:137-49; PMID:24630390; https://doi.org/10.1016/j.diabres.2013.11.002
7. Keating S, El-Osta A. Epigenetic changes in diabetes. Clin Genet 2013; 84:1-10; PMID:23398084; https://doi.org/10.1111/cge.12121
8. Zoghbi HY, Beaudet AL. Epigenetics and Human Disease. Cold Spring Harb Perspect Biol 2016 Feb 1; 8(2):a019497; PMID:26834142; https://doi.org/10.1101/cshperspect.a019497
9. Grimaldi V, De Pascale MR, Zullo A, Soricelli A, Infante T, Mancini FP, Napoli C. Evidence of epigenetic tags in cardiac fibrosis. J Cardiol 2017 Feb; 69(2):401-08; PMID:27863907
10. Ito S, Kuraoka I. Epigenetic modifications in DNA could mimic oxidative DNA damage:A double-edged sword. DNA Repair (Amst) 2015; 32:52-7; PMID:25956859; https://doi.org/10.1016/j.dnarep.2015.04.013
11. Alamdari N, Aversa Z, Castillero E, Hasselgren PO. Acetylation and deacetylation-novel factors in muscle wasting. Metabolism 2013; 62:1-11; PMID:22626763; https://doi.org/10.1016/j.metabol.2012.03.019
12. Arnes L, Sussel L. Epigenetic modifications and long noncoding RNAs influence pancreas development and function. Trends Genet 2015; 31:290-9; PMID:25812926; https://doi.org/10.1016/j.tig.2015.02.008
13. Raghuraman S, Donkin I, Versteyhe S, Barrès R, Simar D. The emerging role of epigenetics in inflammation and immunometabolism. Trends Endocrinol Metab 2016; 27(11):782-795; PMID:27444065; https://doi.org/10.1016/j.tem.2016.06.008
14. Henquin JC. Pathways in beta-cell stimulus-secretion coupling as targets for therapeutic insulin secretagogues. Diabetes 2004; 53:S48-58; PMID:15561921; https://doi.org/10.2337/diabetes.53.suppl_3.S48
15. Yagihashi S, Inaba W, Mizukami H. Dynamic pathology of islet endocrine cells in type 2 diabetes:β-Cell growth, death, regeneration and their clinical implications. J Diabetes Investig 2016; 7:155-65; PMID:27042265; https://doi.org/10.1111/jdi.12424
16. Leibowitz G, Kaiser N, Cerasi E. β -Cell failure in type 2 diabetes. J Diabetes Investig 2011; 2:82-91; PMID:24843466; https://doi.org/10.1111/j.2040-1124.2010.00094.x
17. Johnson JS, Evans-Molina C. Translational implications of the β-cell epigenome in diabetes mellitus. Transl Res 2015; 165:91-101; PMID:24686035; https://doi.org/10.1016/j.trsl.2014.03.002
18. Quilichini E, Haumaitre C. Implication of epigenetics in pancreas development and disease. Best Pract Res Clin Endocrinol Metab 2015; 29:883-98; PMID:26696517; https://doi.org/10.1016/j.beem.2015.10.010
19. Sosa-Pineda B. The gene Pax4 is an essential regulator of pancreatic beta-cell development. Mol Cells 2004; 18:289-94; PMID:15650323
20. Volkmar M, Dedeurwaerder S, Cunha DA, Ndlovu MN, Defrance M, Deplus R, Calonne E, Volkmar U, Igoillo-Esteve M, Naamane N, et al. DNA methylation profiling identifies epigenetic dysregulation in pancreatic islets from type 2 diabetic patients. EMBO J 2012; 31:1405-26; PMID:22293752; https://doi.org/10.1038/emboj.2011.503
21. Dhawan S, Georgia S, Tschen SI, Fan G, Bhushan A. Pancreatic beta cell identity is maintained by DNA methylation-mediated repression of Arx. Dev Cell 2011; 20:419-29; PMID:21497756; https://doi.org/10.1016/j.devcel.2011.03.012
22. Fu X, Jin L, Wang X, Luo A, Hu J, Zheng X, Tsark WM, Riggs AD, Ku HT, Huang W. MicroRNA-26a targets ten eleven translocation enzymes and is regulated during pancreatic cell differentiation. Proc Natl Acad Sci U S A 2013; 110:17892-7; PMID:24114270; https://doi.org/10.1073/pnas.1317397110
23. Lenoir O, Flosseau K, Ma FX, Blondeau B, Mai A, Bassel-Duby R, Ravassard P, Olson EN, Haumaitre C, Scharfmann R. Specific control of pancreatic endocrine β- and δ-cell mass by class IIa histone deacetylases HDAC4, HDAC5, and HDAC9. Diabetes 2011; 60:2861-71; PMID:21953612; https://doi.org/10.2337/db11-0440
24. Scott RA, Lagou V, Welch RP, Wheeler E, Montasser ME, Luan J, Mägi R, Strawbridge RJ, Rehnberg E, Gustafsson S, et al. Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways. Nat Genet 2012; 44:991-1005; PMID:22885924; https://doi.org/10.1038/ng.2385
25. Morris AP, Voight BF, Teslovich TM, Ferreira T, Segrè AV, Steinthorsdottir V, Strawbridge RJ, Khan H, Grallert H, Mahajan A, et al. Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nat Genet 2012; 44:981-90; PMID:22885922; https://doi.org/10.1038/ng.2383
26. Dechamethakun S, Muramatsu M. Long noncoding RNA variations in cardiometabolic diseases. J Hum Genet 2017 Jan; 62(1):97-104; PMID:27305986; https://doi.org/10.1038/jhg.2016.70
27. Francis J, Babu DA, Deering TG, Chakrabarti SK, Garmey JC, Evans-Molina C, Taylor DG, Mirmira RG. Role of chromatin accessibility in the occupancy and transcription of the insulin gene by the pancreatic and duodenal homeobox factor 1. Mol Endocrinol 2006; 20:3133-45; PMID:16901969; https://doi.org/10.1210/me.2006-0126
28. Mosley AL, Corbett JA, Ozcan S. Glucose regulation of insulin gene expression requires the recruitment of p300 by the beta-cell-specific transcription factor Pdx-1. Mol Endocrinol 2004; 18:2279-90; PMID:15166251; https://doi.org/10.1210/me.2003-0463
29. Hall E, Dayeh T, Kirkpatrick CL, Wollheim CB, Dekker Nitert M, Ling C. DNA methylation of the glucagon-like peptide 1 receptor (GLP1R) in human pancreatic islets. BMC Med Genet 2013; 14:76; PMID:23879380; https://doi.org/10.1186/1471-2350-14-76
30. FDA. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm513602.htm/; 2016 [accessed 05.09.16]
31. Ling C, Del Guerra S, Lupi R, Rönn T, Granhall C, Luthman H, Masiello P, Marchetti P, Groop L, Del Prato S. Epigenetic regulation of PPARGC1A in human type 2 diabetic islets and effect on insulin secretion. Diabetologia 2008; 51:615-22; PMID:18270681; https://doi.org/10.1007/s00125-007-0916-5
32. Lysy PA, Corritore E, Sokal EM. New insights into diabetes cell therapy. Curr Diab Rep 2016 May; 16(5):38; PMID:26983626; https://doi.org/10.1007/s11892-016-0729-3
33. Grimaldi V, Schiano C, Casamassimi A, Zullo A, Soricelli A, Mancini FP, Napoli C. Imaging techniques to evaluate cell therapy in peripheral artery disease:state of the art and clinical trials. Clin Physiol Funct Imaging 2016 May; 36(3):165-78; PMID:25385089; https://doi.org/10.1111/cpf.12210
34. Heng BC, Heinimann K, Miny P, Iezzi G, Glatz K, Scherberich A, Zulewski H, Fussenegger M. mRNA transfection-based, feeder-free, induced pluripotent stem cells derived from adipose tissue of a 50-year-old patient. Metab Eng 2013; 18:9-24; PMID:23542141; https://doi.org/10.1016/j.ymben.2013.02.004
35. Saxena P, Heng BC, Bai P, Folcher M, Zulewski H, Fussenegger M. A programmable synthetic lineage-control network that differentiates human IPSCs into glucose-sensitive insulin-secreting beta-like cells. Nat Commun 2016; 7:11247; PMID:27063289; https://doi.org/10.1038/ncomms11247
36. Zhu S, Russ HA, Wang X, Zhang M, Ma T, Xu T, Tang S, Hebrok M, Ding S. Human pancreatic beta-like cells converted from fibroblasts. Nat Commun 2016; 7:10080; PMID:26733021; https://doi.org/10.1038/ncomms10080
37. Ludwig B, Reichel A, Steffen A, Zimerman B, Schally AV, Block NL, Colton CK, Ludwig S, Kersting S, Bonifacio E, et al. Transplantation of human islets without immunosuppression. Proc Natl Acad Sci USA 2013; 110:19054-58; PMID:24167261; https://doi.org/10.1073/pnas.1317561110
38. Scharp DW, Marchetti P. Encapsulated islets for diabetes therapy:history, current progress, and critical issues requiring solution. Adv Drug Deliv Rev 2014; 67-68:35-73; PMID:23916992; https://doi.org/10.1016/j.addr.2013.07.018
39. Quiskamp N, Bruin JE, Kieffer TJ. Differentiation of human pluripotent stem cells into β-cells:Potential and challenges. Best Pract Res Clin Endocrinol Metab 2015; 29:833-847; PMID:26696513; https://doi.org/10.1016/j.beem.2015.10.011
40. Khodabandehloo H, Gorgani-Firuzjaee S, Panahi S, Meshkani R. Molecular and cellular mechanisms linking inflammation to insulin resistance and β-cell dysfunction. Transl Res 2015 pii:S1931-5244(15)00297-2 2016; 167:228-56; PMID:26408801; https://doi.org/10.1016/j.trsl.2015.08.011
41. Prattichizzo F, Giuliani A, Ceka A, Rippo MR, Bonfigli AR, Testa R, Procopio AD, Olivieri F. Epigenetic mechanisms of endothelial dysfunction in type 2 diabetes. Clin Epigenetics 2015; 7:56; PMID:26015812; https://doi.org/10.1186/s13148-015-0090-4
42. Brasacchio D, Okabe J, Tikellis C, Balcerczyk A, George P, Baker EK, Calkin AC, Brownlee M, Cooper ME, El-Osta A. Hyperglycemia induces a dynamic cooperativity of histone methylase and demethylase enzymes associated with gene-activating epigenetic marks that coexist on the lysine tail. Diabetes 2009; 58:1229-36; PMID:19208907; https://doi.org/10.2337/db08-1666
43. Nilsson E, Jansson PA, Perfilyev A, Volkov P, Pedersen M, Svensson MK, Poulsen P, Ribel-Madsen R, Pedersen NL, Almgren P, et al. Altered DNA methylation and differential expression of genes influencing metabolism and inflammation in adipose tissue from subjects with type 2 diabetes. Diabetes 2014; 63:2962-76; PMID:24812430; https://doi.org/10.2337/db13-1459
44. Remely M, Aumueller E, Jahn D, Hippe B, Brath H, Haslberger AG. Microbiota and epigenetic regulation of inflammatory mediators in type 2 diabetes and obesity. Benef Microbes 2014; 5:33-43; PMID:24533976; https://doi.org/10.3920/BM2013.006
45. Stefan N, Häring HU, Hu FB, Schulze MB. Metabolically healthy obesity:epidemiology, mechanisms, and clinical implications. Lancet Diabetes Endocrinol 2013; 1:152-62; PMID:24622321; https://doi.org/10.1016/S2213-8587(13)70062-7
46. Guénard F, Tchernof A, Deshaies Y, Pérusse L, Biron S, Lescelleur O, Biertho L, Marceau S, Vohl MC. Differential methylation in visceral adipose tissue of obese men discordant for metabolic disturbances. Physiol Genomics 2014; 46:216-22; PMID:24495915; https://doi.org/10.1152/physiolgenomics.00160.2013
47. Ortega FJ, Moreno M, Mercader JM, Moreno-Navarrete JM, Fuentes-Batllevell N, Sabater M, Ricart W, Fernández-Real JM. Inflammation triggers specific microRNA profiles in human adipocytes and macrophages and in their supernatants. Clin Epigenetics 2015; 7:49; PMID:25926893; https://doi.org/10.1186/s13148-015-0083-3
48. Nesca V, Guay C, Jacovetti C, Menoud V, Peyot ML, Laybutt DR, Prentki M, Regazzi R. Identification of particular groups of microRNAs that positively or negatively impact on beta cell function in obese models of type 2 diabetes. Diabetologia 2013; 56:2203-12; PMID:23842730; https://doi.org/10.1007/s00125-013-2993-y
49. Roggli E, Britan A, Gattesco S, Lin-Marq N, Abderrahmani A, Meda P, Regazzi R. Involvement of microRNAs in the cytotoxic effects exerted by proinflammatory cytokines on pancreatic β-cells. Diabetes 2010; 59:978-86; PMID:20086228; https://doi.org/10.2337/db09-0881
50. Heneghan HM, Miller N, McAnena OJ, O'Brien T, Kerin MJ. Differential miRNA expression in omental adipose tissue and in the circulation of obese patients identifies novel metabolic biomarkers. J Clin Endocrinol Metab 2011; 96:E846-E850; PMID:21367929; https://doi.org/10.1210/jc.2010-2701
51. Zhao X, Mohan R, Özcan S, Tang X. MicroRNA-30d induces insulin transcription factor MafA and insulin production by targeting mitogen-activated protein 4 kinase 4 (MAP4K4) in pancreatic β-cells. J Biol Chem 2012; 287:31155-64; PMID:22733810; https://doi.org/10.1074/jbc.M112.362632
52. Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha:direct role in obesity-linked insulin resistance. Science 1993; 259:87-91; PMID:7678183; https://doi.org/10.1126/science.7678183
53. Hotamisligil GS. Inflammation and metabolic disorders. Nature 2006; 444:860-7; PMID:17167474; https://doi.org/10.1038/nature05485
54. Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 2003; 112:1821-30; PMID:14679177; https://doi.org/10.1172/JCI200319451
55. Arner E, Mejhert N, Kulyté A, Balwierz PJ, Pachkov M, Cormont M, Lorente-Cebrián S, Ehrlund A, Laurencikiene J, Hedén P, et al. Adipose tissue microRNAs as regulators of CCL2 production in human obesity. Diabetes 2012; 61:1986-93; PMID:22688341; https://doi.org/10.2337/db11-1508
56. Wang D, Garcia-Bassets I, Benner C, Li W, Su X, Zhou Y, Qiu J, Liu W, Kaikkonen MU, Ohgi KA, et al. Reprogramming transcription by distinct classes of enhancers functionally defined by eRNA. Nature 2011; 474:390-4; PMID:21572438; https://doi.org/10.1038/nature10006
57. Zhu X, Wu YB, Zhou J, Kang DM. Upregulation of lncRNA MEG3 promotes hepatic insulin resistance via increasing FoxO1 expression. Biochem Biophys Res Commun 2016; 469:319-25; PMID:26603935; https://doi.org/10.1016/j.bbrc.2015.11.048
58. Dhliwayo N, Sarras MP, Jr, Luczkowski E, Mason SM, Intine RV. Parp inhibition prevents ten-eleven translocase enzyme activation and hyperglycemia-induced DNA demethylation. Diabetes 2014 Sep; 63(9):3069-76; PMID:24722243; https://doi.org/10.2337/db13-1916
59. Napoli C, Crudele V, Soricelli A, Al-Omran M, Vitale N, Infante T, Mancini FP. Primary prevention of atherosclerosis:a clinical challenge for the reversal of epigenetic mechanisms? Circulation 2012; 125:2363-73; PMID:22586291; https://doi.org/10.1161/CIRCULATIONAHA.111.085787
60. Heard E, Martienssen RA. Transgenerational epigenetic inheritance:myths and mechanisms. Cell 2014; 157:95-109; PMID:24679529; https://doi.org/10.1016/j.cell.2014.02.045
61. Stegemann R, Buchner DA. Transgenerational inheritance of metabolic disease. Semin Cell Dev Biol 2015; 43:131-40; PMID:25937492; https://doi.org/10.1016/j.semcdb.2015.04.007
62. Torrens C, Poston L, Hanson MA. Transmission of raised blood pressure and endothelial dysfunction to the F2 generation induced by maternal protein restriction in the F0, in the absence of dietary challenge in the F1 generation. Br J Nutr 2008; 100:760-6; PMID:18304387; https://doi.org/10.1017/S0007114508921747
63. Zullo A, Casamassimi A, Mancini FP, Napoli C. Cardiovascular disease and transgenerational epigenetic effects. In:Tollefsbol T, editor. Transgenerational Epigenetics. Evidence and Debate, San Diego:Academic Press; 2014, p. 321-341; https://doi.org/10.1016/B978-0-12-405944-3.01001-1
64. Barker DJ, Hales CN, Fall CH, Osmond C, Phipps K, Clark PM. Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X):relation to reduced fetal growth. Diabetologia 1993; 36:62-7; PMID:8436255; https://doi.org/10.1007/BF00399095
65. Gluckman PD, Hanson MA. Living with the past:evolution, development, and patterns of disease. Science 2004; 305:1733-6; PMID:15375258; https://doi.org/10.1126/science.1095292
66. Ma RC, Tutino GE, Lillycrop KA, Hanson MA, Tam WH. Maternal diabetes, gestational diabetes and the role of epigenetics in their long term effects on offspring. Prog Biophys Mol Biol 2015; 118:55-68; PMID:25792090; https://doi.org/10.1016/j.pbiomolbio.2015.02.010
67. Baz B, Riveline JP, Gautier JF. Endocrinology of pregnancy:Gestational diabetes mellitus:definition, aetiological and clinical aspects. Eur J Endocrinol 2016; 174:R43-51; PMID:26431552; https://doi.org/10.1530/EJE-15-0378
68. Liu C, Lu L, Kong Q, Li Y, Wu H, Yang W, Xu S, Yang X, Song X, Yang JY, et al. Developing discriminate model and comparative analysis of differentially expressed genes and pathways for bloodstream samples of diabetes mellitus type 2. BMC Bioinformatics 2014; 15(Suppl 17):S5; PMID:25559614; https://doi.org/10.1186/1471-2105-15-S17-S5
69. Zhang W, Chen Y, Sun F, Jiang R. Domain RBF:a Bayesian regression approach to the prioritization of candidate domains for complex diseases. BMC Syst Biol 2011; 5:55; PMID:21504591; https://doi.org/10.1186/1752-0509-5-55
70. Wang W, Zhang W, Jiang R, Luan Y. Prioritisation of associations between protein domains and complex diseases using domain-domain interaction networks. IET Syst Biol 2010; 4:212-22; PMID:20500001; https://doi.org/10.1049/iet-syb.2009.0037
71. Zhao C, Mao J, Ai J, Shenwu M, Shi T, Zhang D, Wang X, Wang Y, Deng Y. Integrated lipidomics and transcriptomic analysis of peripheral blood reveals significantly enriched pathways in type 2 diabetes mellitus. BMC Med Genomics 2013; 6(Suppl 1):S12; PMID:23369247; https://doi.org/10.1186/1755-8794-6-S1-S12
72. Li F, Xu Y, Shang D, Yang H, Liu W, Han J, Sun Z, Yao Q, Zhang C, Ma J, et al. MPINet:metabolite pathway identification via coupling of global metabolite network structure and metabolomic profile. Biomed Res Int 2014; 2014:325697; PMID:25057481; https://doi.org/10.1155/2014/325697
73. Yousri NA, Mook-Kanamori DO, Selim MM, Takiddin AH, Al-Homsi H, Al-Mahmoud KA, Karoly ED, Krumsiek J, Do KT, Neumaier U, et al. A systems view of type 2 diabetes-associated metabolic perturbations in saliva, blood and urine at different timescales of glycaemic control. Diabetologia 2015; 58:1855-67; PMID:26049400; https://doi.org/10.1007/s00125-015-3636-2
74. Ali O, Cerjak D, Kent JW, Jr, James R, Blangero J, Carless MA, Zhang Y. An epigenetic map of age-associated autosomal loci in northern European families at high risk for the metabolic syndrome. Clin Epigenetics 2015; 7:12; PMID:25806089; https://doi.org/10.1186/s13148-015-0048-6
75. Liu H, Wang T, Liu H, Wei Y, Zhao G, Su J, Wu Q, Qiao H, Zhang Y. Detection of type 2 diabetes related modules and genes based on epigenetic networks. BMC Syst Biol 2014; 8(Suppl 1):S5; PMID:24565181; https://doi.org/10.1186/1752-0509-8-5
76. Xavier DJ, Takahashi P, Evangelista AF, Foss-Freitas MC, Foss MC, Donadi EA, Passos GA, Sakamoto-Hojo ET. Assessment of DNA damage and mRNA/miRNA transcriptional expression profiles in hyperglycemic versus non-hyperglycemic patients with type 2 diabetes mellitus. Mutat Res 2015; 776:98-110; PMID:26364207; https://doi.org/10.1016/j.mrfmmm.2015.01.016
77. Ghaedi H, Bastami M, Jahani MM, Alipoor B, Tabasinezhad M, Ghaderi O, Nariman-Saleh-Fam Z, Mirfakhraie R, Movafagh A, Omrani MD, et al. A bioinformatics approach to the identification of variants associated with Type 1 and Type 2 diabetes mellitus that reside in functionally validated mirnas binding sites. Biochem Genet 2016; 54:211-21; PMID:26820452; https://doi.org/10.1007/s10528-016-9713-5
78. Arguelles AO, Meruvu S, Bowman JD, Choudhury M. Are epigenetic drugs for diabetes and obesity at our door step? Drug Discov Today 2016; 21:499-509; PMID:26697737; https://doi.org/10.1016/j.drudis.2015.12.001
79. Balasubramanyam K, Altaf M, Varier RA, Swaminathan V, Ravindran A, Sadhale PP, Kundu TK. Polyisoprenylated benzophenone, garcinol, a natural histone acetyltransferase inhibitor, represses chromatin transcription and alters global gene expression. J Biol Chem 2004; 279:33716-26; PMID:15155757; https://doi.org/10.1074/jbc.M402839200
80. Kadiyala CS, Zheng L, Du Y, Yohannes E, Kao HY, Miyagi M, Kern TS. 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 2012; 287:25869-80; PMID:22648458; https://doi.org/10.1074/jbc.M112.375204
81. Tedong L, Madiraju P, Martineau LC, Vallerand D, Arnason JT, Desire DD, Lavoie L, Kamtchouing P, Haddad PS. Hydro-ethanolic extract of cashew tree (Anacardium occidentale) nut and its principal compound, anacardic acid, stimulate glucose uptake in C2C12 muscle cells. Mol Nutr Food Res 2010; 54:1753-62; PMID:20603833; https://doi.org/10.1002/mnfr.201000045
82. Zhang DW, Fu M, Gao SH, Liu JL. Curcumin and diabetes:a systematic review. Evid Based Complement Alternat Med 2013; 636053; PMID:24348712; https://doi.org/10.1155/2013/636053
83. Yun JM, Jialal I, Devaraj S. Epigenetic regulation of high glucose-induced proinflammatory cytokine production in monocytes by curcumin. J Nutr Biochem 2011; 22:450-8; PMID:20655188; https://doi.org/10.1016/j.jnutbio.2010.03.014
84. Wickenberg J, Ingemansson SL, Hlebowicz J. Effects of Curcuma longa (turmeric) on postprandial plasma glucose and insulin in healthy subjects. Nutr J 2010; 9:43; PMID:20937162; https://doi.org/10.1186/1475-2891-9-43
85. Chous AP, Richer SP, Gerson JD, Kowluru RA. The Diabetes Visual Function Supplement Study (DiVFuSS). Br J Ophthalmol 2016; 100(2):227-34; PMID:26089210; https://doi.org/10.1136/bjophthalmol-2014-306534
86. Christensen DP, Dahllöf M, Lundh M, Rasmussen DN, Nielsen MD, Billestrup N, Grunnet LG, Mandrup-Poulsen T. Histone deacetylase (HDAC) inhibition as a novel treatment for diabetes mellitus. Mol Med 2011; 17:378-90; PMID:21274504; https://doi.org/10.2119/molmed.2011.00021
87. Galmozzi A, Mitro N, Ferrari A, Gers E, Gilardi F, Godio C, Cermenati G, Gualerzi A, Donetti E, Rotili D, et al. Inhibition of class I histone deacetylases unveils a mitochondrial signature and enhances oxidative metabolism in skeletal muscle and adipose tissue. Diabetes 2013; 62:732-42; PMID:23069623; https://doi.org/10.2337/db12-0548
88. Gao Z, Yin J, Zhang J, Ward RE, Martin RJ, Lefevre M, Cefalu WT, Ye J. Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes 2009; 58:1509-17; PMID:19366864; https://doi.org/10.2337/db08-1637
89. Henagan TM, Stefanska B, Fang Z, Navard AM, Ye J, Lenard NR, Devarshi PP. Sodium butyrate epigenetically modulates high fat diet-induced skeletal muscle mitochondrial adaptation, obesity and insulin resistance through nucleosome positioning. Br J Pharmacol 2015; 172:2782-98; PMID:25559882; https://doi.org/10.1111/bph.13058
90. Lenoir O, Flosseau K, Ma FX, Blondeau B, Mai A, Bassel-Duby R, Ravassard P, Olson EN, Haumaitre C, Scharfmann R. Specific control of pancreatic endocrine β- and δ-cell mass by class IIa histone deacetylases HDAC4, HDAC5, and HDAC9. Diabetes 2011; 60:2861-71; PMID:21953612; https://doi.org/10.2337/db11-0440
91. Dahllöf MS, Christensen DP, Lundh M, Dinarello CA, Mascagni P, Grunnet LG, Mandrup-Poulsen T. The lysine deacetylase inhibitor Givinostat inhibits β-cell IL-1β induced IL-1β transcription and processing. Islets 2012; 4:417-22; PMID:23486342; https://doi.org/10.4161/isl.23541
92. Vitiello M, Zullo A, Servillo L, Mancini FP, Borriello A, Giovane A, Della Ragione F, D'Onofrio N, Balestrieri ML. Multiple pathways of SIRT6 at the crossroads in the control of longevity, cancer, and cardiovascular diseases. Ageing Res Rev 2016 pii:S1568-1637(16)30181-7; PMID:27829173
93. Chung S, Yao H, Caito S, Hwang JW, Arunachalam G, Rahman I. Regulation of SIRT1 in cellular functions:role of polyphenols. Arch Biochem Biophys 2010; 501:79-90; PMID:20450879; https://doi.org/10.1016/j.abb.2010.05.003
94. Caton PW, Nayuni NK, Kieswich J, Khan NQ, Yaqoob MM, Corder R. Metformin suppresses hepatic gluconeogenesis through induction of SIRT1 and GCN5. J Endocrinol 2010; 205:97-106; PMID:20093281; https://doi.org/10.1677/JOE-09-0345
95. Goldberg RB, Rosenson RS, Hernandez-Triana E, Misir S, Jones MR. Initial combination therapy with metformin plus colesevelam improves lipoprotein particles in patients with early type 2 diabetes mellitus. J Clin Lipidol 2012; 6:318-24; PMID:22836068; https://doi.org/10.1016/j.jacl.2012.05.005
96. Chen LL, Zhang HH, Zheng J, Hu X, Kong W, Hu D, Wang SX, Zhang P. Resveratrol attenuates high-fat diet-induced insulin resistance by influencing skeletal muscle lipid transport and subsarcolemmal mitochondrial beta oxidation. Metabolism 2011; 60:1598-609; PMID:21632075
97. Vetterli L, Brun T, Giovannoni L, Bosco D, Maechler P. Resveratrol potentiates glucose stimulated insulin secretion in INS-1E beta-cells and human islets through a SIRT1-dependent mechanism. J Biol Chem 2011; 286:6049-60; PMID:21163946; https://doi.org/10.1074/jbc.M110.176842
98. Novelle MG, Wahl D, Diéguez C, Bernier M, de Cabo R. Resveratrol supplementation:Where are we now and where should we go? Ageing Res Rev 2015; 21:1-15; PMID:25625901; https://doi.org/10.1016/j.arr.2015.01.002
99. Milne JC, Lambert PD, Schenk S, Carney DP, Smith JJ, Gagne DJ, Jin L, Boss O, Perni RB, Vu CB, et al. Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature 2007; 450:712-6; PMID:18046409; https://doi.org/10.1038/nature06261
100. Most J, Goossens GH, Jocken JW, Blaak EE. Short-term supplementation with a specific combination of dietary polyphenols increases energy expenditure and alters substrate metabolism in overweight subjects. Int J Obes (Lond) 2014 May; 38(5):698-706; PMID:24317366; https://doi.org/10.1038/ijo.2013.231
101. Liu K, Zhou R, Wang B, Mi MT. Effect of resveratrol on glucose control and insulin sensitivity:a meta-analysis of 11 randomized controlled trials. Am J Clin Nutr 2014 Jun; 99(6):1510-9; PMID:24695890; https://doi.org/10.3945/ajcn.113.082024
102. Broderick JA, Zamore PD. MicroRNA therapeutics. Gene Therapy 2011; 18:1104-10; PMID:21525952; https://doi.org/10.1038/gt.2011.50
103. Kolfschoten IG, Roggli E, Nesca V, Regazzi R. Role and therapeutic potential of microRNAs in diabetes. Diabetes Obes Metab 2009; 11(Suppl 4):118-29; PMID:19817794; https://doi.org/10.1111/j.1463-1326.2009.01118.x
104. El Ouaamari A, Baroukh N, Martens GA, Lebrun P, Pipeleers D, van Obberghen E. miR-375 targets 3′-phosphoinositide-dependent protein kinase-1 and regulates glucose-induced biological responses in pancreatic β-cells. Diabetes 2008; 57:2708-17; PMID:18591395; https://doi.org/10.2337/db07-1614
105. Trajkovski M, Hausser J, Soutschek J, Bhat B, Akin A, Zavolan M, Heim MH, Stoffel M. MicroRNAs 103 and 107 regulate insulin sensitivity. Nature 2011; 474:649-53; PMID:21654750; https://doi.org/10.1038/nature10112
106. Lovis P, Roggli E, Laybutt DR, Gattesco S, Yang JY, Widmann C, Abderrahmani A, Regazzi R. Alterations in microRNA expression contribute to fatty acid-induced pancreatic β-cell dysfunction. Diabetes 2008; 57:2728-36; PMID:18633110; https://doi.org/10.2337/db07-1252
107. Grimaldi V, Mancini FP, Casamassimi A, Al-Omran M, Zullo A, Infante T, Napoli C. Potential benefits of cell therapy in coronary heart disease. J Cardiol 2013; 62:267-76; PMID:23834957; https://doi.org/10.1016/j.jjcc.2013.05.017
108. Gaw A. A new reality:achieving cholesterol-lowering goals in clinical practice. Atherosclerosis 2002; 2:S5-S8; https://doi.org/10.1016/S1567-5688(01)00018-6
109. Napoli C, Infante T, Casamassimi A. Maternal-foetal epigenetic interactions in the beginning of cardiovascular damage. Cardiovasc Res 2011; 92:367-74; PMID:21764886; https://doi.org/10.1093/cvr/cvr201
110. Dje N'Guessan P, Riediger F, Vardarova K, Scharf S, Eitel J, Opitz B, Slevogt H, Weichert W, Hocke AC, Schmeck B, et al. Statins control oxidized LDL-mediated histone modifications and gene expression in cultured human endothelial cells. Arterioscler Thromb Vasc Biol 2009; 29:380-6; PMID:19122173; https://doi.org/10.1161/ATVBAHA.108.178319
111. Betteridge DJ, Carmena R. The diabetogenic action of statins - mechanisms and clinical implications. Nat Rev Endocrinol 2016; 12:99-110; PMID:26668119; https://doi.org/10.1038/nrendo.2015.194
112. Sattar N, Preiss D, Murray HM, Welsh P, Buckley BM, de Craen AJ, Seshasai SR, McMurray JJ, Freeman DJ, Jukema JW, et al. Statins and risk of incident diabetes:a collaborative meta analysis of randomised statin trials. Lancet 2010; 375:735-42; PMID:20167359; https://doi.org/10.1016/S0140-6736(09)61965-6
113. Fujii T, Onimaru M, Yonemitsu Y, Kuwano H, Sueishi K. Statins restore ischemic limb blood flow in diabetic microangiopathy via eNOS/NO upregulation but not via PDGF-BB expression. Am J Physiol Heart Circ Physiol 2008; 294:H2785-H2791; PMID:18441206; https://doi.org/10.1152/ajpheart.00149.2008
114. Bhavsar S, Mudaliar S, Cherrington A. Evolution of exenatide as a diabetes therapeutic. Curr Diabetes Rev 2013; 9:161-93; PMID:23256660; https://doi.org/0.2174/1573399811309020007
115. Yasuda H, Mizukami K, Hayashi M, Kamiya T, Hara H, Adachi T. Exendin-4 promotes extracellular-superoxide dismutase expression in A549 cells through DNA demethylation. J Clin Biochem Nutr 2016; 58:34-9; PMID:26798195; https://doi.org/10.3164/jcbn.15-16