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The Egyptian Journal of Internal Medicine
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Epigenetics and diabetes mellitus

The Egyptian Journal of Internal Medicine volume 28, pages 39–51 (2016)Cite this article

Abstract

Epigenetic mechanisms were shown to be involved in the control of endocrine cell fate decision, islet differentiation, β-cell identity, proliferation, and mature function. The pathologic mechanisms involved in the development of type 1 diabetes may include DNA methylation, histone modification, microRNA, and molecular mimicry. These mechanisms may act through the regulation of gene expression.

References

  1. Zimmet PZ, Magliano DJ, Herman WH, Shaw JE. Diabetes: a 21st century challenge. Lancet Diabetes Endocrinol 2014; 2: 56–64.

    PubMed  Google Scholar 

  2. Bruce KD. Maternal and in utero determinants of type 2 diabetes risk in the young. Curr Diab Rep 2014; 14: 446.

    Google Scholar 

  3. Ruiz MA, Chakrabarti S. MicroRNAs: the underlying mediators of pathogenetic processes in vascular complications of diabetes. Can J Diabetes 2013; 37: 339–344.

    PubMed  Google Scholar 

  4. Cheng Z, Almeida FA. Mitochondrial alteration in type 2 diabetes and obesity: an epigenetic link. Cell Cycle 2014; 13: 890–897.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Liu H, Wang T, Liu H, Wei Y, Zhao G, Su J, et al. Detection of type 2 diabetes related modules and genes based on epigenetic networks. BMC Syst Biol 2014; 8: S5.

    PubMed  PubMed Central  Google Scholar 

  6. Ding GL, Wang FF, Shu J, Tian S, Jiang Y, Zhang D, et al. Transgenerational glucose intolerance with Igf2/H19 epigenetic alterations in mouse islet induced by intrauterine hyperglycemia. Diabetes 2012; 61: 1133–1142.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Sterns JD, Smith CB, Steele JR, Stevenson KL, Gallicano GI. Epigenetics and type II diabetes mellitus: underlying mechanisms of prenatal predisposition. Front Cell Dev Biol 2014; 2: 15.

    PubMed  PubMed Central  Google Scholar 

  8. Jiang X, Ma H, Wang Y, Liu Y. Early life factors and type 2 diabetes mellitus. J Diabetes Res 2013; 1: 485082.

    Google Scholar 

  9. Wu YL, Ding YP, Gao J, Tanaka Y, Zhang W. Risk factors and primary prevention trials for type 1 diabetes. Int J Biol Sci 2013; 9: 666–679.

    PubMed  PubMed Central  Google Scholar 

  10. Stankov K, Benc D, Draskovic D. Genetic and epigenetic factors in etiology of diabetes mellitus type 1. Pediatrics 2013; 132: 1112–1122.

    PubMed  Google Scholar 

  11. Xie Z, Chang C, Zhou Z. Molecular mechanisms in autoimmune type 1 diabetes: a critical review. Clin Rev Allergy Immunol 2014; 47: 174–192

    CAS  PubMed  Google Scholar 

  12. Kido Y. Progress in diabetes [Article in Japanese]. Rinsho Byori 2013; 61: 941–947.

    CAS  PubMed  Google Scholar 

  13. Pullen TJ, Rutter GA. Could lncRNAs contribute to β-cell identity and its loss in type 2 diabetes? Biochem Soc Trans 2013; 41: 797–801.

    CAS  PubMed  Google Scholar 

  14. Yan J1, Yang H. Gestational diabetes mellitus, programming and epigenetics. J Matern Fetal Neonatal Med 2013; 27: 1266–1269.

    PubMed  Google Scholar 

  15. Feuer SK, Liu X, Donjacour A, Lin W, Simbulan RK, Giritharan G, et al. Use of a mouse in vitro fertilization model to understand the developmental origins of health and disease hypothesis. Endocrinology 2014; 155: 1956–1969.

    PubMed  PubMed Central  Google Scholar 

  16. Singhal A. The global epidemic of noncommunicable disease: the role of early-life factors. Nestle Nutr Inst Workshop Ser 2014; 78: 123–132.

    PubMed  Google Scholar 

  17. Haumaitre C. Epigenetic regulation of pancreatic islets. Curr Diab Rep 2013; 13: 624–632.

    CAS  PubMed  Google Scholar 

  18. Lui JC, Chen W, Cheung CS, Baron J. Broad shifts in gene expression during early postnatal life are associated with shifts in histone methylation patterns. PLoS One 2014; 9: e86957.

    PubMed  PubMed Central  Google Scholar 

  19. Jufvas A, Sjödin S, Lundqvist K, Amin R, Vener AV, Strålfors P. Global differences in specific histone H3 methylation are associated with overweight and type 2 diabetes. Clin Epigenetics 2013; 5: 15.

    PubMed  PubMed Central  Google Scholar 

  20. Dayeh T, Volkov P, Salö S, Hall E, Nilsson E, Olsson AH, et al. Genomewide DNA methylation analysis of human pancreatic islets from type 2 diabetic and non-diabetic donors identifies candidate genes that influence insulin secretion. PLoS Genet 2014; 10: e1004160.

    PubMed  PubMed Central  Google Scholar 

  21. Stefan M, Zhang W, Concepcion E, Yi Z, Tomer Y. DNA methylation profiles in type 1 diabetes twins point to strong epigenetic effects on etiology. J Autoimmun 2014; 50: 33–37.

    CAS  PubMed  Google Scholar 

  22. Khan S, Jena GB. Protective role of sodium butyrate, a HDAC inhibitor on beta-cell proliferation, function and glucose homeostasis through modulation of p38/ERK MAPK and apoptotic pathways: study in juvenile diabetic rat. Chem Biol Interact 2014; 213: 1–12.

    CAS  PubMed  Google Scholar 

  23. Fiorino E, Giudici M, Ferrari A, Mitro N, Caruso D, De Fabiani E, et al. The sirtuin class of histone deacetylases: regulation and roles in lipid metabolism. IUBMB Life 2014; 66: 89–99.

    CAS  PubMed  Google Scholar 

  24. Kupczyk M, Kuna P. MicroRNAs, new biomarkers of respiratory tract diseases [Article in Polish]. Pneumonol Alergol Pol 2014; 82: 183–190.

    CAS  PubMed  Google Scholar 

  25. Kaspi H, Pasvolsky R, Hornstein E. Could microRNAs contribute to the maintenance of β cell identity? Trends Endocrinol Metab 2014; 25: 285–292.

    CAS  PubMed  Google Scholar 

  26. Kameswaran V, Bramswig NC, McKenna LB, Penn M, Schug J, Hand NJ, et al. Epigenetic regulation of the DLK1-MEG3 microRNA cluster in human type 2 diabetic islets. Cell Metab 2014; 19: 135–145.

    CAS  PubMed  Google Scholar 

  27. Martínez JA, Milagro FI, Claycombe KJ, Schalinske KL. Epigenetics in adipose tissue, obesity, weight loss, and diabetes. Adv Nutr 2014; 5: 71–81.

    PubMed  PubMed Central  Google Scholar 

  28. Jang H, Serra C. Nutrition, epigenetics, and diseases. Clin Nutr Res 2014; 3: 1–8.

    PubMed  PubMed Central  Google Scholar 

  29. Ruchat SM, Hivert MF, Bouchard L. Epigenetic programming of obesity and diabetes by in utero exposure to gestational diabetes mellitus. Nutr Rev 2013; 71: S88–S94.

    PubMed  Google Scholar 

  30. Tarry-Adkins JL, Ozanne SE. The impact of early nutrition on the ageing trajectory. Proc Nutr Soc 2014; 73: 289–301.

    CAS  PubMed  Google Scholar 

  31. Mathias PC, Elmhiri G, de Oliveira JC, Delayre-Orthez C, Barella LF, Tófolo LP, et al. Maternal diet, bioactive molecules, and exercising as reprogramming tools of metabolic programming. Eur J Nutr 2014; 53: 711–722.

    CAS  PubMed  Google Scholar 

  32. Zhang X, Yang R, Jia Y, Cai D, Zhou B, Qu, X et al. Hypermethylation of Sp1 binding site suppresses hypothalamic POMC in neonates and may contribute to metabolic disorders in adults: impact of maternal dietary CLAs. Diabetes 2014; 63: 1475–1487.

    CAS  PubMed  Google Scholar 

  33. Schwenk RW, Vogel H, Schürmann A. Genetic and epigenetic control of metabolic health. Mol Metab 2013; 2: 337–347.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Dick KJ, Nelson CP, Tsaprouni L, Sandling JK, Aïssi D, Wahl S, et al. DNA methylation and body-mass index: a genome-wide analysis. Lancet 2014; 383: 1990–1998.

    CAS  PubMed  Google Scholar 

  35. Uebel K, Pusch K, Gedrich K, Schneider KT, Hauner H, Bader BL. Effect of maternal obesity with and without gestational diabetes on offspring subcutaneous and preperitoneal adipose tissue development from birth up to year-1. BMC Pregnancy Childbirth 2014; 14: 138.

    PubMed  PubMed Central  Google Scholar 

  36. Attig L, Vigé A, Gabory A, Karimi M, Beauger A, Gross MS. Dietary alleviation of maternal obesity and diabetes: increased resistance to diet-induced obesity transcriptional and epigenetic signatures. PLoS One 2013; 8: e66816.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Toubal A, Treuter E, Clément K, Venteclef N. Genomic and epigenomic regulation of adipose tissue inflammation in obesity. Trends Endocrinol Metab 2013; 24: 625–634.

    CAS  PubMed  Google Scholar 

  38. Nicholas LM, Rattanatray L, MacLaughlin SM, Ozanne SE, Kleemann DO, Walker SK, et al. Differential effects of maternal obesity and weight loss in the periconceptional period on the epigenetic regulation of hepatic insulinsignaling pathways in the offspring. FASEB J 2013; 27: 3786–3796.

    CAS  PubMed  Google Scholar 

  39. Ruchat SM, Houde AA, Voisin G, St-Pierre J, Perron P, Baillargeon JP, et al. Gestational diabetes mellitus epigenetically affects genes predominantly involved in metabolic diseases. Epigenetics 2013; 8: 935–943.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Del Rosario MC, Ossowski V, Knowler WC, Bogardus C, Baier LJ, Hanson RL. Potential epigenetic dysregulation of genes associated with maturity onset diabetes of the young and type 2diabetes in humans exposed to a diabetic intrauterine environment: an analysis of genome-wide DNA methylation. Metabolism 2014; 63: 654–660.

    PubMed  PubMed Central  Google Scholar 

  41. Dumesic DA, Goodarzi MO, Chazenbalk GD, Abbott DH. Intrauterine environment and polycystic ovary syndrome. Semin Reprod Med 2014; 32: 159–165.

    PubMed  PubMed Central  Google Scholar 

  42. Langley-Evans SC. Nutrition in early life and the programming of adult disease: a review. J Hum Nutr Diet 2015; 28: 1–14.

    PubMed  Google Scholar 

  43. Jacobsen SC, Gillberg L, Bork-Jensen J, Ribel-Madsen R, Lara E, Calvanese V, et al. Young men with low birthweight exhibit decreased plasticity of genome-wide muscle DNA methylation by high-fat overfeeding. Diabetologia 2014; 57: 1154–1158.

    CAS  PubMed  Google Scholar 

  44. Lambrot R, Xu C, Saint-Phar S, Chountalos G, Cohen T, Paquet M, et al. Low paternal dietary folate alters the mouse sperm epigenome and is associated with negative pregnancy outcomes. Nat Commun 2013; 4: 2889.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Wei Y, Yang CR, Wei YP, Zhao ZA, Hou Y, Schatten H, et al. Paternally induced transgenerational inheritance of susceptibility to diabetes in mammals. Proc Natl Acad Sci USA 2014; 111: 1873–1878.

    CAS  PubMed  Google Scholar 

  46. Tang ZH, Fang Z, Zhou L. Human genetics of diabetic vascular complications. J Genet 2013; 92: 677–694.

    CAS  PubMed  Google Scholar 

  47. Xu Y. Transcriptional regulation of endothelial dysfunction in atherosclerosis: anepigenetic perspective. J Biomed Res 2014; 28: 47–52.

    CAS  PubMed  Google Scholar 

  48. Kowluru RA, Santos JM, Mishra M. Epigenetic modifications and diabetic retinopathy. Biomed Res Int 2013; 2013: 635284.

    PubMed  PubMed Central  Google Scholar 

  49. Zeng J, Chen B. Epigenetic mechanisms in the pathogenesis of diabetic retinopathy. Ophthalmologica 2014; 232: 1–9.

    CAS  PubMed  Google Scholar 

  50. Reddy MA, Tak Park J, Natarajan R. Epigenetic modifications in the pathogenesis of diabetic nephropathy. Semin Nephrol 2013; 33: 341–353.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Lin CL, Lee PH, Hsu YC, Lei CC, Ko JY, Chuang PC, et al. MicroRNA-29a promotion of nephrin acetylation ameliorates hyperglycemia-induced podocyte dysfunction. J Am Soc Nephrol 2014; 25: 1698–1709.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Mellor KM, Brimble MA, Delbridge LM. Glucose as an agent of post-translational modification in diabetes – new cardiacepigenetic insights. Life Sci 2014; 129: 48–53.

    PubMed  Google Scholar 

  53. Vecellio M, Spallotta F, Nanni S, Colussi C, Cencioni C, Derlet A, et al. The histone acetylase activator pentadecylidenemalonate 1b rescues proliferation and differentiation in human cardiac mesenchymal cells of type 2 diabetic patients. Diabetes 2014; 63: 2132–2147.

    CAS  PubMed  Google Scholar 

  54. Ling C, Rönn T. Epigenetic adaptation to regular exercise in humans. Drug Discov Today 2014; 19: 1015–1018.

    CAS  PubMed  Google Scholar 

  55. Laker RC, Lillard TS, Okutsu M, Zhang M, Hoehn KL, Connelly JJ, et al. Exercise prevents maternal high-fat diet-induced hypermethylation of the pgc-1α gene and age-dependent metabolic dysfunction in the offspring. Diabetes 2014; 63: 1605–1611.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Santos JM, Tewari S, Benite-Ribeiro SA. The effect of exercise on epigenetic modifications of PGC1: the impact on type 2 diabetes. Med Hypotheses 2014; 82: 748–753.

    CAS  PubMed  Google Scholar 

  57. Dogan MV, Shields B, Cutrona C, Gao L, Gibbons FX, Simons R, et al. The effect of smoking on DNA methylation of peripheral blood mononuclear cells from African American women. BMC Genomics 2014; 15: 1471–2164.

    Google Scholar 

  58. Pandian GN, Taniguchi J, Sugiyama H. Cellular reprogramming for pancreatic β-cell regeneration: clinical potential of small molecule control. Clin Transl Med 2014; 3: 6.

    PubMed  PubMed Central  Google Scholar 

  59. Pennarossa G, Maffei S, Campagnol M, Tarantini L, Gandolfi F, Brevini TA. Brief demethylation step allows the conversion of adult human skin fibroblasts into insulin-secreting cells. Proc Natl Acad Sci USA 2013; 110: 8948–8953.

    CAS  PubMed  Google Scholar 

  60. Miao F, Chen Z, Genuth S, Paterson A, Zhang L, Wu X, et al. Evaluating the role of epigenetic histone modifications in the metabolic memory of type 1 diabetes. Diabetes 2014; 63: 1748–1762.

    CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Internal Medicine Department, Faculty of Medicine, Beni Suef University, 62511, Beni Suef City, Egypt

    Mohammed K. Rehan MD

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  1. Mohammed K. Rehan MD
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Correspondence to Mohammed K. Rehan MD.

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Rehan, M.K. Epigenetics and diabetes mellitus. Egypt J Intern Med 28, 39–51 (2016). https://doi.org/10.4103/1110-7782.193890

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