{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:25:24Z","timestamp":1792783524206,"version":"4.5.0"},"reference-count":92,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"University of Athens","id":[{"id":"https:\/\/ror.org\/04gnjpq42","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Hormones"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Type 2 diabetes mellitus (T2DM) develops through the interplay of insulin resistance and progressive beta-cell dysfunction. Beyond genetic predisposition, epigenetic regulation provides a mechanistic link between environmental exposures (e.g., overnutrition, physical inactivity, inflammation) and durable changes in gene expression in pancreatic islets and insulin-sensitive tissues (skeletal muscle, adipose tissue, and liver). Accordingly, this review aims to synthesize current evidence on the epigenetic mechanisms underlying T2DM and its complications, with a particular focus on epigenetically targeted therapeutic strategies. We summarize major epigenetic processes, including DNA and RNA methylation, histone post-translational modifications, and non-coding RNAs, and discuss how these alterations remodel chromatin and transcriptional programs under metabolic stress. A key concept is \u201cmetabolic memory,\u201d whereby transient hyperglycemia or lipotoxicity can induce persistent epigenetic signatures that sustain dysfunctional cellular phenotypes, partly shaped by mitochondrial metabolism and Krebs cycle intermediates regulating chromatin-modifying enzymes. Importantly, several epigenetic alterations demonstrate partial reversibility following lifestyle modification, metabolic surgery, or pharmacological intervention (e.g., DNA methyltransferase inhibition), underscoring their therapeutic relevance. Finally, we address translational challenges, including limited access to human tissues and inadequate modeling of chronic metabolic stress, which currently constrain clinical exploitation of epigenetic targets in T2DM.<\/jats:p>","DOI":"10.1007\/s42000-026-00829-5","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:52:57Z","timestamp":1790085177000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Epigenetic modifications in type 2 diabetes mellitus"],"prefix":"10.1007","author":[{"given":"Marina","family":"Spaho","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fotios","family":"Karytis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stavros P.","family":"Papadakos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7039-4223","authenticated-orcid":false,"given":"Antonios","family":"Chatzigeorgiou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"829_CR1","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/S0140-6736(23)01301-6","volume":"402","author":"KL Ong","year":"2023","unstructured":"Ong KL, Stafford LK, McLaughlin SA, Boyko EJ, Vollset SE, Smith AE et al (2023) Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021. Lancet 402:203\u2013234. https:\/\/doi.org\/10.1016\/S0140-6736(23)01301-6","journal-title":"Lancet"},{"key":"829_CR2","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1093\/ndt\/gfaf177","volume":"41","author":"BB Duncan","year":"2025","unstructured":"Duncan BB, Magliano DJ, Boyko EJ (2025) IDF Diabetes Atlas 11th edition 2025: global prevalence and projections for 2050. Nephrol Dial Transpl 41:7\u20139. https:\/\/doi.org\/10.1093\/ndt\/gfaf177","journal-title":"Nephrol Dial Transpl"},{"key":"829_CR3","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1186\/s12943-020-01197-3","volume":"19","author":"Y Lu","year":"2020","unstructured":"Lu Y, Chan Y-T, Tan H-Y, Li S, Wang N, Feng Y (2020) Epigenetic regulation in human cancer: the potential role of epi-drug in cancer therapy. Mol Cancer 19:79. https:\/\/doi.org\/10.1186\/s12943-020-01197-3","journal-title":"Mol Cancer"},{"key":"829_CR4","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1016\/j.mce.2013.04.002","volume":"382","author":"L Groop","year":"2014","unstructured":"Groop L, Pociot F (2014) Genetics of diabetes \u2013 are we missing the genes or the disease? Mol Cell Endocrinol 382:726\u2013739. https:\/\/doi.org\/10.1016\/j.mce.2013.04.002","journal-title":"Mol Cell Endocrinol"},{"key":"829_CR5","doi-asserted-by":"publisher","DOI":"10.1002\/cph4.70003","volume":"15","author":"A Singh","year":"2025","unstructured":"Singh A, Shadangi S, Gupta PK, Rana S (2025) Type 2 diabetes mellitus: a comprehensive review of pathophysiology, comorbidities, and emerging therapies. Compr Physiol 15:e70003. https:\/\/doi.org\/10.1002\/cph4.70003","journal-title":"Compr Physiol"},{"key":"829_CR6","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1007\/s00335-020-09839-z","volume":"31","author":"D Kaspar","year":"2020","unstructured":"Kaspar D, Hastreiter S, Irmler M, Hrab\u00e9 de Angelis M, Beckers J (2020) Nutrition and its role in epigenetic inheritance of obesity and diabetes across generations. Mamm Genome 31:119\u2013133. https:\/\/doi.org\/10.1007\/s00335-020-09839-z","journal-title":"Mamm Genome"},{"key":"829_CR7","doi-asserted-by":"publisher","first-page":"838","DOI":"10.4161\/epi.6.7.16537","volume":"6","author":"MK Skinner","year":"2011","unstructured":"Skinner MK (2011) Environmental epigenetic transgenerational inheritance and somatic epigenetic mitotic stability. Epigenetics 6:838\u2013842. https:\/\/doi.org\/10.4161\/epi.6.7.16537","journal-title":"Epigenetics"},{"key":"829_CR8","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1007\/s11892-019-1168-8","volume":"19","author":"S Dhawan","year":"2019","unstructured":"Dhawan S, Natarajan R (2019) Epigenetics and type 2 diabetes risk. Curr Diab Rep 19:47. https:\/\/doi.org\/10.1007\/s11892-019-1168-8","journal-title":"Curr Diab Rep"},{"key":"829_CR9","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.114815","volume":"43","author":"P Wang","year":"2024","unstructured":"Wang P, Chen L-L, Xiong Y, Ye D (2024) Metabolite regulation of epigenetics in cancer. Cell Rep 43:114815. https:\/\/doi.org\/10.1016\/j.celrep.2024.114815","journal-title":"Cell Rep"},{"key":"829_CR10","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1038\/nrendo.2016.87","volume":"12","author":"R Barr\u00e8s","year":"2016","unstructured":"Barr\u00e8s R, Zierath JR (2016) The role of diet and exercise in the transgenerational epigenetic landscape of T2DM. Nat Rev Endocrinol 12:441\u2013451. https:\/\/doi.org\/10.1038\/nrendo.2016.87","journal-title":"Nat Rev Endocrinol"},{"key":"829_CR11","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1111\/imm.13207","volume":"161","author":"CJ Lio","year":"2020","unstructured":"Lio CJ, Huang SC (2020) Circles of life: linking metabolic and epigenetic cycles to immunity. Immunology 161:165\u2013174. https:\/\/doi.org\/10.1111\/imm.13207","journal-title":"Immunology"},{"key":"829_CR12","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.arr.2014.05.004","volume":"16","author":"A Salminen","year":"2014","unstructured":"Salminen A, Kauppinen A, Hiltunen M, Kaarniranta K (2014) Krebs cycle intermediates regulate DNA and histone methylation: epigenetic impact on the aging process. Ageing Res Rev 16:45\u201365. https:\/\/doi.org\/10.1016\/j.arr.2014.05.004","journal-title":"Ageing Res Rev"},{"key":"829_CR13","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1038\/npp.2012.112","volume":"38","author":"LD Moore","year":"2013","unstructured":"Moore LD, Le T, Fan G (2013) DNA methylation and its basic function. Neuropsychopharmacology 38:23\u201338. https:\/\/doi.org\/10.1038\/npp.2012.112","journal-title":"Neuropsychopharmacology"},{"key":"829_CR14","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1038\/nrc3895","volume":"15","author":"L Yang","year":"2015","unstructured":"Yang L, Rau R, Goodell MA (2015) DNMT3A in haematological malignancies. Nat Rev Cancer 15:152\u2013165. https:\/\/doi.org\/10.1038\/nrc3895","journal-title":"Nat Rev Cancer"},{"key":"829_CR15","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1038\/s41392-023-01537-x","volume":"8","author":"X Zhang","year":"2023","unstructured":"Zhang X, Zhang Y, Wang C, Wang X (2023) TET (ten-eleven translocation) family proteins: structure, biological functions and applications. Signal Transduct Target Ther 8:297. https:\/\/doi.org\/10.1038\/s41392-023-01537-x","journal-title":"Signal Transduct Target Ther"},{"key":"829_CR16","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1038\/s41580-019-0168-5","volume":"20","author":"S Zaccara","year":"2019","unstructured":"Zaccara S, Ries RJ, Jaffrey SR (2019) Reading, writing and erasing mRNA methylation. Nat Rev Mol Cell Biol 20:608\u2013624. https:\/\/doi.org\/10.1038\/s41580-019-0168-5","journal-title":"Nat Rev Mol Cell Biol"},{"key":"829_CR17","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1038\/cr.2011.22","volume":"21","author":"AJ Bannister","year":"2011","unstructured":"Bannister AJ, Kouzarides T (2011) Regulation of chromatin by histone modifications. Cell Res 21:381\u2013395. https:\/\/doi.org\/10.1038\/cr.2011.22","journal-title":"Cell Res"},{"key":"829_CR18","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1016\/j.cell.2007.05.009","volume":"129","author":"A Barski","year":"2007","unstructured":"Barski A, Cuddapah S, Cui K, Roh T-Y, Schones DE, Wang Z et al (2007) High-resolution profiling of histone methylations in the human genome. Cell 129:823\u2013837. https:\/\/doi.org\/10.1016\/j.cell.2007.05.009","journal-title":"Cell"},{"key":"829_CR19","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1016\/j.tibs.2013.09.004","volume":"38","author":"H-M Herz","year":"2013","unstructured":"Herz H-M, Garruss A, Shilatifard A (2013) SET for life: biochemical activities and biological functions of SET domain-containing proteins. Trends Biochem Sci 38:621\u2013639. https:\/\/doi.org\/10.1016\/j.tibs.2013.09.004","journal-title":"Trends Biochem Sci"},{"key":"829_CR20","doi-asserted-by":"publisher","first-page":"dev181180","DOI":"10.1242\/dev.181180","volume":"146","author":"M Ninova","year":"2019","unstructured":"Ninova M, Fejes T\u00f3th K, Aravin AA (2019) The control of gene expression and cell identity by H3K9 trimethylation. Development 146:dev181180. https:\/\/doi.org\/10.1242\/dev.181180","journal-title":"Development"},{"key":"829_CR21","doi-asserted-by":"publisher","DOI":"10.1126\/science.aac4383","volume":"350","author":"L Jiao","year":"2015","unstructured":"Jiao L, Liu X (2015) Structural basis of histone H3K27 trimethylation by an active polycomb repressive complex 2. Science 350:aac4383. https:\/\/doi.org\/10.1126\/science.aac4383","journal-title":"Science"},{"key":"829_CR22","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1038\/s41580-022-00566-8","volume":"24","author":"JS Mattick","year":"2023","unstructured":"Mattick JS, Amaral PP, Carninci P, Carpenter S, Chang HY, Chen L-L et al (2023) Long non-coding RNAs: definitions, functions, challenges and recommendations. Nat Rev Mol Cell Biol 24:430\u2013447. https:\/\/doi.org\/10.1038\/s41580-022-00566-8","journal-title":"Nat Rev Mol Cell Biol"},{"key":"829_CR23","doi-asserted-by":"publisher","first-page":"C367","DOI":"10.1152\/ajpcell.00051.2022","volume":"323","author":"LT Dalgaard","year":"2022","unstructured":"Dalgaard LT, S\u00f8rensen AE, Hardikar AA, Joglekar MV (2022) The microRNA-29 family: role in metabolism and metabolic disease. Am J Physiol Cell Physiol 323:C367\u2013C377. https:\/\/doi.org\/10.1152\/ajpcell.00051.2022","journal-title":"Am J Physiol Cell Physiol"},{"key":"829_CR24","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25115678","volume":"25","author":"A Brandt","year":"2024","unstructured":"Brandt A, Kopp F (2024) Long noncoding RNAs in diet-induced metabolic diseases. Int J Mol Sci 25:5678. https:\/\/doi.org\/10.3390\/ijms25115678","journal-title":"Int J Mol Sci"},{"key":"829_CR25","doi-asserted-by":"publisher","first-page":"10181","DOI":"10.2147\/CMAR.S276022","volume":"12","author":"S Fu","year":"2020","unstructured":"Fu S, Wang Y, Li H, Chen L, Liu Q (2020) Regulatory networks of lncRNA MALAT-1 in cancer. Cancer Manag Res 12:10181\u201310198. https:\/\/doi.org\/10.2147\/CMAR.S276022","journal-title":"Cancer Manag Res"},{"key":"829_CR26","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11102909","volume":"11","author":"J Xiao","year":"2022","unstructured":"Xiao J, Joseph S, Xia M, Teng F, Chen X, Huang R et al (2022) Circular RNAs acting as miRNAs\u2019 sponges and their roles in stem cells. J Clin Med 11:2909. https:\/\/doi.org\/10.3390\/jcm11102909","journal-title":"J Clin Med"},{"key":"829_CR27","doi-asserted-by":"publisher","first-page":"111264","DOI":"10.1016\/j.mce.2021.111264","volume":"529","author":"H-Y Wu","year":"2021","unstructured":"Wu H-Y, Cheng Y, Jin L-Y, Zhou Y, Pang H-Y, Zhu H et al (2021) Paternal obesity impairs hepatic gluconeogenesis of offspring by altering Igf2\/H19 DNA methylation. Mol Cell Endocrinol 529:111264. https:\/\/doi.org\/10.1016\/j.mce.2021.111264","journal-title":"Mol Cell Endocrinol"},{"key":"829_CR28","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1038\/s41392-022-01073-0","volume":"7","author":"M Li","year":"2022","unstructured":"Li M, Chi X, Wang Y, Setrerrahmane S, Xie W, Xu H (2022) Trends in insulin resistance: insights into mechanisms and therapeutic strategy. Signal Transduct Target Ther 7:216. https:\/\/doi.org\/10.1038\/s41392-022-01073-0","journal-title":"Signal Transduct Target Ther"},{"key":"829_CR29","doi-asserted-by":"publisher","first-page":"4367","DOI":"10.4049\/jimmunol.1300038","volume":"191","author":"J Phieler","year":"2013","unstructured":"Phieler J, Chung K-J, Chatzigeorgiou A, Klotzsche-von Ameln A, Garcia-Martin R, Sprott D et al (2013) The complement anaphylatoxin C5a receptor contributes to obese adipose tissue inflammation and insulin resistance. J Immunol 191:4367\u20134374. https:\/\/doi.org\/10.4049\/jimmunol.1300038","journal-title":"J Immunol"},{"key":"829_CR30","doi-asserted-by":"publisher","first-page":"2583","DOI":"10.1007\/s00125-012-2607-0","volume":"55","author":"A Chatzigeorgiou","year":"2012","unstructured":"Chatzigeorgiou A, Karalis KP, Bornstein SR, Chavakis T (2012) Lymphocytes in obesity-related adipose tissue inflammation. Diabetologia 55:2583\u20132592. https:\/\/doi.org\/10.1007\/s00125-012-2607-0","journal-title":"Diabetologia"},{"key":"829_CR31","doi-asserted-by":"publisher","first-page":"2686","DOI":"10.1073\/pnas.1400419111","volume":"111","author":"A Chatzigeorgiou","year":"2014","unstructured":"Chatzigeorgiou A, Seijkens T, Zarzycka B, Engel D, Poggi M, van den Berg S et al (2014) Blocking CD40-TRAF6 signaling is a therapeutic target in obesity-associated insulin resistance. Proc Natl Acad Sci U S A 111:2686\u20132691. https:\/\/doi.org\/10.1073\/pnas.1400419111","journal-title":"Proc Natl Acad Sci U S A"},{"key":"829_CR32","doi-asserted-by":"publisher","first-page":"681649","DOI":"10.3389\/fendo.2021.681649","volume":"12","author":"S Andrade","year":"2021","unstructured":"Andrade S, Morais T, Sandovici I, Seabra AL, Const\u00e2ncia M, Monteiro MP (2021) Adipose tissue epigenetic profile in obesity-related dysglycemia \u2013 a systematic review. Front Endocrinol (Lausanne) 12:681649. https:\/\/doi.org\/10.3389\/fendo.2021.681649","journal-title":"Front Endocrinol (Lausanne)"},{"key":"829_CR33","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/j.molmet.2019.04.009","volume":"25","author":"AG Kerr","year":"2019","unstructured":"Kerr AG, Sinha I, Dadvar S, Arner P, Dahlman I (2019) Epigenetic regulation of diabetogenic adipose morphology. Mol Metab 25:159\u2013167. https:\/\/doi.org\/10.1016\/j.molmet.2019.04.009","journal-title":"Mol Metab"},{"key":"829_CR34","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1080\/21623945.2021.1978157","volume":"10","author":"E Mirzaeicheshmeh","year":"2021","unstructured":"Mirzaeicheshmeh E, Zerrweck C, Centeno-Cruz F, Baca-Peynado P, Martinez-Hernandez A, Garc\u00eda-Ortiz H et al (2021) Alterations of DNA methylation during adipogenesis differentiation of mesenchymal stem cells isolated from adipose tissue of patients with obesity is associated with type 2 diabetes. Adipocyte 10:493\u2013504. https:\/\/doi.org\/10.1080\/21623945.2021.1978157","journal-title":"Adipocyte"},{"key":"829_CR35","doi-asserted-by":"publisher","DOI":"10.1038\/s41387-022-00228-w","volume":"12","author":"P Baca","year":"2022","unstructured":"Baca P, Barajas-Olmos F, Mirzaeicheshmeh E, Zerrweck C, Guilbert L, S\u00e1nchez EC et al (2022) DNA methylation and gene expression analysis in adipose tissue to identify new loci associated with T2D development in obesity. Nutr Diabetes 12:50. https:\/\/doi.org\/10.1038\/s41387-022-00228-w","journal-title":"Nutr Diabetes"},{"key":"829_CR36","doi-asserted-by":"publisher","first-page":"2090","DOI":"10.3390\/cells12162090","volume":"12","author":"L Parrillo","year":"2023","unstructured":"Parrillo L, Spinelli R, Longo M, Zatterale F, Santamaria G, Leone A et al (2023) The transcription factor HOXA5: novel insights into metabolic diseases and adipose tissue dysfunction. Cells 12:2090. https:\/\/doi.org\/10.3390\/cells12162090","journal-title":"Cells"},{"key":"829_CR37","doi-asserted-by":"publisher","DOI":"10.3390\/ijms242115673","volume":"24","author":"L Kovac","year":"2023","unstructured":"Kovac L, Speckmann T, J\u00e4hnert M, Gottmann P, Fritsche L, H\u00e4ring H-U et al (2023) Identification of microRNAs associated with prediabetic status in obese women. Int J Mol Sci 24:15673. https:\/\/doi.org\/10.3390\/ijms242115673","journal-title":"Int J Mol Sci"},{"key":"829_CR38","doi-asserted-by":"publisher","first-page":"17447","DOI":"10.3390\/ijms242417447","volume":"24","author":"K Gutowska","year":"2023","unstructured":"Gutowska K, Ko\u017aniewski K, W\u0105sowski M, Jonas MI, Bartoszewicz Z, Lisik W et al (2023) AGER-1 long non-coding RNA levels correlate with the expression of the advanced glycosylation end-product receptor, a regulator of the inflammatory response in visceral adipose tissue of women with obesity and type 2 diabetes mellitus. Int J Mol Sci 24:17447. https:\/\/doi.org\/10.3390\/ijms242417447","journal-title":"Int J Mol Sci"},{"key":"829_CR39","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.681356","volume":"12","author":"H Maude","year":"2021","unstructured":"Maude H, Sanchez-Cabanillas C, Cebola I (2021) Epigenetics of hepatic insulin resistance. Front Endocrinol (Lausanne) 12:681356. https:\/\/doi.org\/10.3389\/fendo.2021.681356","journal-title":"Front Endocrinol (Lausanne)"},{"key":"829_CR40","doi-asserted-by":"publisher","first-page":"1683","DOI":"10.1080\/17460441.2025.2579124","volume":"20","author":"SP Papadakos","year":"2025","unstructured":"Papadakos SP, Georgiadou C, Kassi E, Velliou R-I, Chatzigeorgiou A (2025) Animal models of lean metabolic dysfunction-associated steatotic liver disease (MASLD): bridging pathogenesis and novel drug discovery. Expert Opin Drug Discov 20:1683\u20131700. https:\/\/doi.org\/10.1080\/17460441.2025.2579124","journal-title":"Expert Opin Drug Discov"},{"key":"829_CR41","doi-asserted-by":"publisher","first-page":"E1491","DOI":"10.1210\/jc.2015-3204","volume":"100","author":"E Nilsson","year":"2015","unstructured":"Nilsson E, Matte A, Perfilyev A, de Mello VD, K\u00e4kel\u00e4 P, Pihlajam\u00e4ki J et al (2015) Epigenetic alterations in human liver from subjects with type 2 diabetes in parallel with reduced folate levels. J Clin Endocrinol Metab 100:E1491\u2013E1501. https:\/\/doi.org\/10.1210\/jc.2015-3204","journal-title":"J Clin Endocrinol Metab"},{"key":"829_CR42","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1016\/j.phrs.2016.09.009","volume":"113","author":"S Sharma","year":"2016","unstructured":"Sharma S, Taliyan R (2016) Histone deacetylase inhibitors: future therapeutics for insulin resistance and type 2 diabetes. Pharmacol Res 113:320\u2013326. https:\/\/doi.org\/10.1016\/j.phrs.2016.09.009","journal-title":"Pharmacol Res"},{"key":"829_CR43","doi-asserted-by":"publisher","first-page":"1861","DOI":"10.2337\/db18-1861-P","volume":"67","author":"SW G\u00f6rgens","year":"2018","unstructured":"G\u00f6rgens SW, Raichur S, Wohlfart P, Brunner B, Tennagels N, Bielohuby M (2018) Liver-specific siRNA inhibition of class 2a histone deacetylases (HDACs) reduces expression of genes regulating gluconeogenesis in primary human and mouse hepatocytes, but not in mice. Diabetes 67:1861\u2013P. https:\/\/doi.org\/10.2337\/db18-1861-P","journal-title":"Diabetes"},{"key":"829_CR44","doi-asserted-by":"publisher","first-page":"2182","DOI":"10.1007\/s00125-020-05212-6","volume":"63","author":"C Krause","year":"2020","unstructured":"Krause C, Gei\u00dfler C, Tackenberg H, El Gammal AT, Wolter S, Spranger J, Mann O, Lehnert H, Kirchner H (2020) Multi-layered epigenetic regulation of IRS2 expression in the liver of obese individuals with type 2 diabetes. Diabetologia 63:2182\u20132193. https:\/\/doi.org\/10.1007\/s00125-020-05212-6","journal-title":"Diabetologia"},{"key":"829_CR45","doi-asserted-by":"publisher","first-page":"1310","DOI":"10.2337\/db17-1539","volume":"67","author":"A Abderrahmani","year":"2018","unstructured":"Abderrahmani A, Yengo L, Caiazzo R, Canouil M, Cauchi S, Raverdy V et al (2018) Increased hepatic PDGF-AA signaling mediates liver insulin resistance in obesity-associated type 2 diabetes. Diabetes 67:1310\u20131321. https:\/\/doi.org\/10.2337\/db17-1539","journal-title":"Diabetes"},{"key":"829_CR46","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.844707","volume":"13","author":"Y Jiang","year":"2022","unstructured":"Jiang Y, Zhu H, Chen Z, Yu Y-C, Guo X-H, Chen Y et al (2022) Hepatic IGF2\/H19 epigenetic alteration induced glucose intolerance in gestational diabetes mellitus offspring via FoxO1 mediation. Front Endocrinol (Lausanne) 13:844707. https:\/\/doi.org\/10.3389\/fendo.2022.844707","journal-title":"Front Endocrinol (Lausanne)"},{"key":"829_CR47","doi-asserted-by":"publisher","first-page":"2332","DOI":"10.1080\/15592294.2022.2119120","volume":"17","author":"K Ziarniak","year":"2022","unstructured":"Ziarniak K, Yang T, Boycott C, Beetch M, Sassek M, Grzeda E et al (2022) DNA hypermethylation of Kiss1r promoter and reduction of hepatic Kiss1r in female rats with type 2 diabetes. Epigenetics 17:2332\u20132346. https:\/\/doi.org\/10.1080\/15592294.2022.2119120","journal-title":"Epigenetics"},{"key":"829_CR48","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.108352","volume":"26","author":"X Xu","year":"2023","unstructured":"Xu X, Yu C, He H, Pan X, Hou A, Feng J et al (2023) MiR-337-3p improves metabolic-associated fatty liver disease through regulation of glycolipid metabolism. iScience 26:108352. https:\/\/doi.org\/10.1016\/j.isci.2023.108352","journal-title":"iScience"},{"key":"829_CR49","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-024-03789-y","volume":"22","author":"C Ling","year":"2024","unstructured":"Ling C, Vavakova M, Ahmad Mir B, S\u00e4ll J, Perfilyev A, Martin M et al (2024) Multiomics profiling of DNA methylation, microRNA, and mRNA in skeletal muscle from monozygotic twin pairs discordant for type 2 diabetes identifies dysregulated genes controlling metabolism. BMC Med 22:572. https:\/\/doi.org\/10.1186\/s12916-024-03789-y","journal-title":"BMC Med"},{"key":"829_CR50","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0051302","volume":"7","author":"R Ribel-Madsen","year":"2012","unstructured":"Ribel-Madsen R, Fraga MF, Jacobsen S, Bork-Jensen J, Lara E, Calvanese V et al (2012) Genome-wide analysis of DNA methylation differences in muscle and fat from monozygotic twins discordant for type 2 diabetes. PLoS One 7:e51302. https:\/\/doi.org\/10.1371\/journal.pone.0051302","journal-title":"PLoS One"},{"key":"829_CR51","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12081-0","volume":"10","author":"S Gancheva","year":"2019","unstructured":"Gancheva S, Ouni M, Jelenik T, Koliaki C, Szendroedi J, Toledo FGS et al (2019) Dynamic changes of muscle insulin sensitivity after metabolic surgery. Nat Commun 10:4179. https:\/\/doi.org\/10.1038\/s41467-019-12081-0","journal-title":"Nat Commun"},{"key":"829_CR52","doi-asserted-by":"publisher","first-page":"7267910","DOI":"10.1155\/2017\/7267910","volume":"2017","author":"JV Esteves","year":"2017","unstructured":"Esteves JV, Enguita FJ, Machado UF (2017) MicroRNAs-mediated regulation of skeletal muscle GLUT4 expression and translocation in insulin resistance. J Diabetes Res 2017:7267910. https:\/\/doi.org\/10.1155\/2017\/7267910","journal-title":"J Diabetes Res"},{"key":"829_CR53","doi-asserted-by":"publisher","first-page":"1294","DOI":"10.1016\/j.bbadis.2013.03.021","volume":"1832","author":"P Agarwal","year":"2013","unstructured":"Agarwal P, Srivastava R, Srivastava AK, Ali S, Datta M (2013) miR-135a targets IRS2 and regulates insulin signaling and glucose uptake in the diabetic gastrocnemius skeletal muscle. Biochim Biophys Acta Mol Basis Dis 1832:1294\u20131303. https:\/\/doi.org\/10.1016\/j.bbadis.2013.03.021","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"829_CR54","doi-asserted-by":"publisher","first-page":"112109","DOI":"10.1016\/j.envres.2021.112109","volume":"204","author":"H Zhang","year":"2022","unstructured":"Zhang H, Ben Y, Han Y, Zhang Y, Li Y, Chen X (2022) Phthalate exposure and risk of diabetes mellitus: implications from a systematic review and meta-analysis. Environ Res 204:112109. https:\/\/doi.org\/10.1016\/j.envres.2021.112109","journal-title":"Environ Res"},{"key":"829_CR55","doi-asserted-by":"publisher","first-page":"9230","DOI":"10.7150\/thno.45253","volume":"10","author":"J Wei","year":"2020","unstructured":"Wei J, Hao Q, Chen C, Li J, Han X, Lei Z et al (2020) Epigenetic repression of miR-17 contributed to di(2-ethylhexyl) phthalate-triggered insulin resistance by targeting Keap1-Nrf2\/miR-200a axis in skeletal muscle. Theranostics 10:9230\u20139248. https:\/\/doi.org\/10.7150\/thno.45253","journal-title":"Theranostics"},{"key":"829_CR56","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.599651","volume":"11","author":"S Simaitis","year":"2020","unstructured":"Simaitis S, Schulte-K\u00f6rne B, Schiffer T, Bloch W, Predel H-G, Brixius K et al (2020) Evidence for training-induced changes in miRNA levels in the skeletal muscle of patients with type 2 diabetes mellitus. Front Physiol 11:599651. https:\/\/doi.org\/10.3389\/fphys.2020.599651","journal-title":"Front Physiol"},{"key":"829_CR57","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1128\/MCB.00715-14","volume":"35","author":"P Tontonoz","year":"2015","unstructured":"Tontonoz P, Cortez-Toledo O, Wroblewski K, Hong C, Lim L, Carranza R et al (2015) The orphan nuclear receptor Nur77 is a determinant of myofiber size and muscle mass in mice. Mol Cell Biol 35:1125\u20131138. https:\/\/doi.org\/10.1128\/MCB.00715-14","journal-title":"Mol Cell Biol"},{"key":"829_CR58","doi-asserted-by":"publisher","first-page":"2152","DOI":"10.1210\/me.2007-0169","volume":"21","author":"LC Chao","year":"2007","unstructured":"Chao LC, Zhang Z, Pei L, Saito T, Tontonoz P, Pilch PF (2007) Nur77 coordinately regulates expression of genes linked to glucose metabolism in skeletal muscle. Mol Endocrinol 21:2152\u20132163. https:\/\/doi.org\/10.1210\/me.2007-0169","journal-title":"Mol Endocrinol"},{"key":"829_CR59","doi-asserted-by":"publisher","first-page":"12573","DOI":"10.1074\/jbc.M409580200","volume":"280","author":"MA Maxwell","year":"2005","unstructured":"Maxwell MA, Cleasby ME, Harding A, Stark A, Cooney GJ, Muscat GEO (2005) Nur77 regulates lipolysis in skeletal muscle cells. J Biol Chem 280:12573\u201312584. https:\/\/doi.org\/10.1074\/jbc.M409580200","journal-title":"J Biol Chem"},{"key":"829_CR60","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.jnutbio.2018.03.015","volume":"57","author":"J Kasch","year":"2018","unstructured":"Kasch J, Kanzleiter I, Saussenthaler S, Sch\u00fcrmann A, Keijer J, van Schothorst E et al (2018) Insulin sensitivity linked skeletal muscle Nr4a1 DNA methylation is programmed by the maternal diet and modulated by voluntary exercise in mice. J Nutr Biochem 57:86\u201392. https:\/\/doi.org\/10.1016\/j.jnutbio.2018.03.015","journal-title":"J Nutr Biochem"},{"key":"829_CR61","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1007\/s11154-008-9101-5","volume":"9","author":"KJ Chang-Chen","year":"2008","unstructured":"Chang-Chen KJ, Mullur R, Bernal-Mizrachi E (2008) \u03b2-cell failure as a complication of diabetes. Rev Endocr Metab Disord 9:329\u2013343. https:\/\/doi.org\/10.1007\/s11154-008-9101-5","journal-title":"Rev Endocr Metab Disord"},{"key":"829_CR62","doi-asserted-by":"publisher","first-page":"4001","DOI":"10.1172\/JCI129188","volume":"129","author":"LI Hudish","year":"2019","unstructured":"Hudish LI, Reusch JEB, Sussel L (2019) \u03b2 cell dysfunction during progression of metabolic syndrome to type 2 diabetes. J Clin Invest 129:4001\u20134008. https:\/\/doi.org\/10.1172\/JCI129188","journal-title":"J Clin Invest"},{"key":"829_CR63","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1007\/s11892-019-1196-4","volume":"19","author":"AA Christensen","year":"2019","unstructured":"Christensen AA, Gannon M (2019) The beta cell in type 2 diabetes. Curr Diab Rep 19:81. https:\/\/doi.org\/10.1007\/s11892-019-1196-4","journal-title":"Curr Diab Rep"},{"key":"829_CR64","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.2337\/db16-0996","volume":"66","author":"P Volkov","year":"2017","unstructured":"Volkov P, Bacos K, Ofori JK, Esguerra JLS, Eliasson L, R\u00f6nn T et al (2017) Whole-genome bisulfite sequencing of human pancreatic islets reveals novel differentially methylated regions in type 2 diabetes pathogenesis. Diabetes 66:1074\u20131085. https:\/\/doi.org\/10.2337\/db16-0996","journal-title":"Diabetes"},{"key":"829_CR65","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1016\/j.devcel.2011.03.012","volume":"20","author":"S Dhawan","year":"2011","unstructured":"Dhawan S, Georgia S, Tschen S, Fan G, Bhushan A (2011) Pancreatic \u03b2 cell identity is maintained by DNA methylation-mediated repression of Arx. Dev Cell 20:419\u2013429. https:\/\/doi.org\/10.1016\/j.devcel.2011.03.012","journal-title":"Dev Cell"},{"key":"829_CR66","doi-asserted-by":"publisher","first-page":"2851","DOI":"10.1172\/JCI79956","volume":"125","author":"S Dhawan","year":"2015","unstructured":"Dhawan S, Tschen S-I, Zeng C, Guo T, Hebrok M, Matveyenko A et al (2015) DNA methylation directs functional maturation of pancreatic \u03b2 cells. J Clin Invest 125:2851\u20132860. https:\/\/doi.org\/10.1172\/JCI79956","journal-title":"J Clin Invest"},{"key":"829_CR67","doi-asserted-by":"publisher","first-page":"1965","DOI":"10.2337\/db18-0900","volume":"68","author":"E Hall","year":"2019","unstructured":"Hall E, J\u00f6nsson J, Ofori JK, Volkov P, Perfilyev A, Dekker Nitert M et al (2019) Glucolipotoxicity alters insulin secretion via epigenetic changes in human islets. Diabetes 68:1965\u20131974. https:\/\/doi.org\/10.2337\/db18-0900","journal-title":"Diabetes"},{"key":"829_CR68","doi-asserted-by":"publisher","first-page":"14247","DOI":"10.1111\/jcmm.16041","volume":"24","author":"T Wang","year":"2020","unstructured":"Wang T, Liu X, Xie J, Yuan Q, Wang Y (2020) Cask methylation involved in the injury of insulin secretion function caused by interleukin1-\u03b2. J Cell Mol Med 24:14247\u201314256. https:\/\/doi.org\/10.1111\/jcmm.16041","journal-title":"J Cell Mol Med"},{"key":"829_CR69","doi-asserted-by":"publisher","first-page":"355","DOI":"10.2337\/db19-0685","volume":"69","author":"H Kim","year":"2020","unstructured":"Kim H, Yoon B-H, Oh C-M, Lee J, Lee K, Song H et al (2020) PRMT1 is required for the maintenance of mature \u03b2-cell identity. Diabetes 69:355\u2013368. https:\/\/doi.org\/10.2337\/db19-0685","journal-title":"Diabetes"},{"key":"829_CR70","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1007\/s00125-023-05896-6","volume":"66","author":"B Vanderkruk","year":"2023","unstructured":"Vanderkruk B, Maeshima N, Pasula DJ, An M, McDonald CL, Suresh P et al (2023) Methylation of histone H3 lysine 4 is required for maintenance of beta cell function in adult mice. Diabetologia 66:1097\u20131115. https:\/\/doi.org\/10.1007\/s00125-023-05896-6","journal-title":"Diabetologia"},{"key":"829_CR71","doi-asserted-by":"publisher","first-page":"1294","DOI":"10.1016\/j.cmet.2018.04.013","volume":"27","author":"TT-H Lu","year":"2018","unstructured":"Lu TT-H, Heyne S, Dror E, Casas E, Leonhardt L, Boenke T et al (2018) The polycomb-dependent epigenome controls \u03b2 cell dysfunction, dedifferentiation, and diabetes. Cell Metab 27:1294\u20131308e7. https:\/\/doi.org\/10.1016\/j.cmet.2018.04.013","journal-title":"Cell Metab"},{"key":"829_CR72","doi-asserted-by":"publisher","first-page":"2608","DOI":"10.1007\/s00125-018-4735-7","volume":"61","author":"T Nammo","year":"2018","unstructured":"Nammo T, Udagawa H, Funahashi N, Kawaguchi M, Uebanso T, Hiramoto M et al (2018) Genome-wide profiling of histone H3K27 acetylation featured fatty acid signalling in pancreatic beta cells in diet-induced obesity in mice. Diabetologia 61:2608\u20132620. https:\/\/doi.org\/10.1007\/s00125-018-4735-7","journal-title":"Diabetologia"},{"key":"829_CR73","doi-asserted-by":"publisher","first-page":"107231","DOI":"10.1016\/j.isci.2023.107231","volume":"26","author":"F Oger","year":"2023","unstructured":"Oger F, Moreno M, Derhourhi M, Thiroux B, Berberian L, Bourouh C et al (2023) Pharmacological HDAC inhibition impairs pancreatic \u03b2-cell function through an epigenome-wide reprogramming. iScience 26:107231. https:\/\/doi.org\/10.1016\/j.isci.2023.107231","journal-title":"iScience"},{"key":"829_CR74","doi-asserted-by":"publisher","first-page":"2279","DOI":"10.1210\/me.2003-0463","volume":"18","author":"AL Mosley","year":"2004","unstructured":"Mosley AL, Corbett JA, \u00d6zcan S (2004) Glucose regulation of insulin gene expression requires the recruitment of p300 by the \u03b2-cell-specific transcription factor Pdx-1. Mol Endocrinol 18:2279\u20132290. https:\/\/doi.org\/10.1210\/me.2003-0463","journal-title":"Mol Endocrinol"},{"key":"829_CR75","doi-asserted-by":"publisher","first-page":"1265","DOI":"10.1093\/cvr\/cvae100","volume":"120","author":"S Velagapudi","year":"2024","unstructured":"Velagapudi S, Karsai G, Karsai M, Mohammed SA, Montecucco F, Liberale L et al (2024) Inhibition of de novo ceramide synthesis by sirtuin-1 improves beta-cell function and glucose metabolism in type 2 diabetes. Cardiovasc Res 120:1265\u20131278. https:\/\/doi.org\/10.1093\/cvr\/cvae100","journal-title":"Cardiovasc Res"},{"key":"829_CR76","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.113984","volume":"156","author":"D Li","year":"2022","unstructured":"Li D, Zhang L, He Y, Zhou T, Cheng X, Huang W et al (2022) Novel histone post-translational modifications in diabetes and complications of diabetes: the underlying mechanisms and implications. Biomed Pharmacother 156:113984. https:\/\/doi.org\/10.1016\/j.biopha.2022.113984","journal-title":"Biomed Pharmacother"},{"key":"829_CR77","doi-asserted-by":"publisher","first-page":"115877","DOI":"10.1016\/j.ecoenv.2023.115877","volume":"270","author":"D Li","year":"2024","unstructured":"Li D, Zhang L, Yang P, He Y, Zhou T, Cheng X et al (2024) Sodium benzoate induces pancreatic inflammation and \u03b2 cell apoptosis partially via benzoylation. Ecotoxicol Environ Saf 270:115877. https:\/\/doi.org\/10.1016\/j.ecoenv.2023.115877","journal-title":"Ecotoxicol Environ Saf"},{"key":"829_CR78","doi-asserted-by":"publisher","first-page":"102629","DOI":"10.1016\/j.omtn.2025.102629","volume":"36","author":"IM Amine","year":"2025","unstructured":"Amine IM, Salsabil H, Fadil B, Adnane B, Khaoula E (2025) The impact of ncRNAs on type 2 diabetes: a comprehensive review covering molecular mechanisms to clinical applications. Mol Ther Nucleic Acids 36:102629. https:\/\/doi.org\/10.1016\/j.omtn.2025.102629","journal-title":"Mol Ther Nucleic Acids"},{"key":"829_CR79","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.630032","volume":"12","author":"T Chi","year":"2021","unstructured":"Chi T, Lin J, Wang M, Zhao Y, Liao Z, Wei P (2021) Non-coding RNA as biomarkers for type 2 diabetes development and clinical management. Front Endocrinol (Lausanne) 12:630032. https:\/\/doi.org\/10.3389\/fendo.2021.630032","journal-title":"Front Endocrinol (Lausanne)"},{"key":"829_CR80","doi-asserted-by":"publisher","first-page":"2031","DOI":"10.1159\/000487983","volume":"45","author":"N Wang","year":"2018","unstructured":"Wang N, Zhu Y, Xie M, Wang L, Jin F, Li Y et al (2018) Long noncoding RNA Meg3 regulates Mafa expression in mouse beta cells by inactivating Rad21, Smc3 or Sin3\u03b1. Cell Physiol Biochem 45:2031\u20132043. https:\/\/doi.org\/10.1159\/000487983","journal-title":"Cell Physiol Biochem"},{"key":"829_CR81","doi-asserted-by":"publisher","first-page":"e0300965","DOI":"10.1371\/journal.pone.0300965","volume":"19","author":"J Ma","year":"2024","unstructured":"Ma J, Gao R, Xie Q, Pan X, Tong N (2024) Whole transcriptome sequencing analyses of islets reveal ncRNA regulatory networks underlying impaired insulin secretion and increased \u03b2-cell mass in high fat diet-induced diabetes mellitus. PLoS ONE 19:e0300965. https:\/\/doi.org\/10.1371\/journal.pone.0300965","journal-title":"PLoS ONE"},{"key":"829_CR82","doi-asserted-by":"publisher","first-page":"9031","DOI":"10.1080\/21655979.2021.1992333","volume":"12","author":"Y Zhang","year":"2021","unstructured":"Zhang Y, Zhao Q, Su S, Dan L, Li X, Wang Y et al (2021) Comparative analysis of circRNA expression profile and circRNA-miRNA-mRNA regulatory network between palmitic and stearic acid-induced lipotoxicity to pancreatic \u03b2 cells. Bioengineered 12:9031\u20139045. https:\/\/doi.org\/10.1080\/21655979.2021.1992333","journal-title":"Bioengineered"},{"key":"829_CR83","doi-asserted-by":"publisher","first-page":"1761","DOI":"10.3727\/096368911X612521","volume":"21","author":"M Nieto","year":"2012","unstructured":"Nieto M, Hevia P, Garcia E, Klein D, Alvarez-Cubela S, Bravo-Egana V et al (2012) Antisense miR-7 impairs insulin expression in developing pancreas and in cultured pancreatic buds. Cell Transplant 21:1761\u20131774. https:\/\/doi.org\/10.3727\/096368911X612521","journal-title":"Cell Transplant"},{"key":"829_CR84","doi-asserted-by":"publisher","first-page":"256","DOI":"10.2337\/db17-0506","volume":"67","author":"S Jo","year":"2018","unstructured":"Jo S, Chen J, Xu G, Grayson TB, Thielen LA, Shalev A (2018) miR-204 controls glucagon-like peptide 1 receptor expression and agonist function. Diabetes 67:256\u2013264. https:\/\/doi.org\/10.2337\/db17-0506","journal-title":"Diabetes"},{"key":"829_CR85","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2020.154335","volume":"111","author":"Y Sun","year":"2020","unstructured":"Sun Y, Zhou S, Shi Y, Zhou Y, Zhang Y, Liu K et al (2020) Inhibition of miR-153, an IL-1\u03b2-responsive miRNA, prevents beta cell failure and inflammation-associated diabetes. Metabolism 111:154335. https:\/\/doi.org\/10.1016\/j.metabol.2020.154335","journal-title":"Metabolism"},{"key":"829_CR86","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18240\/ijo.2019.01.01","volume":"12","author":"MY Xie","year":"2019","unstructured":"Xie MY, Yang Y, Liu P, Luo Y, Tang SB (2019) 5-aza-2\u2019-deoxycytidine in the regulation of antioxidant enzymes in retinal endothelial cells and rat diabetic retina. Int J Ophthalmol 12:1\u20137. https:\/\/doi.org\/10.18240\/ijo.2019.01.01","journal-title":"Int J Ophthalmol"},{"key":"829_CR87","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/j.kint.2017.01.010","volume":"92","author":"L Zhang","year":"2017","unstructured":"Zhang L, Zhang Q, Liu S, Chen Y, Li R, Lin T et al (2017) DNA methyltransferase 1 may be a therapy target for attenuating diabetic nephropathy and podocyte injury. Kidney Int 92:140\u2013153. https:\/\/doi.org\/10.1016\/j.kint.2017.01.010","journal-title":"Kidney Int"},{"key":"829_CR88","doi-asserted-by":"publisher","first-page":"2345","DOI":"10.1038\/onc.2016.391","volume":"36","author":"T Zhong","year":"2017","unstructured":"Zhong T, Men Y, Lu L, Geng T, Zhou J, Mitsuhashi A et al (2017) Metformin alters DNA methylation genome-wide via the H19\/SAHH axis. Oncogene 36:2345\u20132354. https:\/\/doi.org\/10.1038\/onc.2016.391","journal-title":"Oncogene"},{"key":"829_CR89","doi-asserted-by":"publisher","first-page":"16489","DOI":"10.1096\/fj.202000860RR","volume":"34","author":"L Scisciola","year":"2020","unstructured":"Scisciola L, Rizzo MR, Cataldo V, Fontanella RA, Balestrieri ML, D\u2019Onofrio N, Marfella R, Paolisso G, Barbieri M (2020) Incretin drugs effect on epigenetic machinery: new potential therapeutic implications in preventing vascular diabetic complications. FASEB J 34:16489\u201316503. https:\/\/doi.org\/10.1096\/fj.202000860RR","journal-title":"FASEB J"},{"key":"829_CR90","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1016\/j.bcp.2011.07.065","volume":"82","author":"TO Khor","year":"2011","unstructured":"Khor TO, Huang Y, Wu T-Y, Shu L, Lee J, Kong A-NT (2011) Pharmacodynamics of curcumin as DNA hypomethylation agent in restoring the expression of Nrf2 via promoter CpGs demethylation. Biochem Pharmacol 82:1073\u20131078. https:\/\/doi.org\/10.1016\/j.bcp.2011.07.065","journal-title":"Biochem Pharmacol"},{"key":"829_CR91","doi-asserted-by":"publisher","first-page":"1398","DOI":"10.1016\/j.bcp.2013.02.010","volume":"85","author":"C Zhang","year":"2013","unstructured":"Zhang C, Su Z-Y, Khor TO, Shu L, Kong A-NT (2013) Sulforaphane enhances Nrf2 expression in prostate cancer TRAMP C1 cells through epigenetic regulation. Biochem Pharmacol 85:1398\u20131404. https:\/\/doi.org\/10.1016\/j.bcp.2013.02.010","journal-title":"Biochem Pharmacol"},{"key":"829_CR92","doi-asserted-by":"publisher","first-page":"2489","DOI":"10.1172\/JCI118308","volume":"96","author":"A De Vos","year":"1995","unstructured":"De Vos A, Heimberg H, Quartier E, Huypens P, Bouwens L, Pipeleers D, Schuit F (1995) Human and rat beta cells differ in glucose transporter but not in glucokinase gene expression. J Clin Invest 96:2489\u20132495. https:\/\/doi.org\/10.1172\/JCI118308","journal-title":"J Clin Invest"}],"container-title":["Hormones"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s42000-026-00829-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s42000-026-00829-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s42000-026-00829-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:52:59Z","timestamp":1790085179000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s42000-026-00829-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,22]]},"references-count":92,"alternative-id":["829"],"URL":"https:\/\/doi.org\/10.1007\/s42000-026-00829-5","relation":{},"ISSN":["1109-3099","2520-8721"],"issn-type":[{"value":"1109-3099","type":"print"},{"value":"2520-8721","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,22]]},"assertion":[{"value":"24 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 September 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 September 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable. This article is a narrative review and did not involve human participants, animals, or identifiable personal data.","order":1,"name":"Ethics","label":"Ethics approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable","order":2,"name":"Ethics","label":"Consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable","order":3,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no competing financial or non-financial interests that are relevant to the content of this article.","order":4,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}]}}