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Endocrine, Metabolic & Immune Disorders - Drug Targets


ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Review Article

Insights into the Role of DNA Methylation and Protein Misfolding in Diabetes Mellitus

Author(s): Sara M. Ahmed, Dina Johar, Mohamed Medhat Ali and Nagwa El-Badri*

Volume 19 , Issue 6 , 2019

Page: [744 - 753] Pages: 10

DOI: 10.2174/1871530319666190305131813

Price: $65


Background: Diabetes mellitus is a metabolic disorder that is characterized by impaired glucose tolerance resulting from defects in insulin secretion, insulin action, or both. Epigenetic modifications, which are defined as inherited changes in gene expression that occur without changes in gene sequence, are involved in the etiology of diabetes.

Methods: In this review, we focused on the role of DNA methylation and protein misfolding and their contribution to the development of both type 1 and type 2 diabetes mellitus.

Results: Changes in DNA methylation in particular are highly associated with the development of diabetes. Protein function is dependent on their proper folding in the endoplasmic reticulum. Defective protein folding and consequently their functions have also been reported to play a role. Early treatment of diabetes has proven to be of great benefit, as even transient hyperglycemia may lead to pathological effects and complications later on. This has been explained by the theory of the development of a metabolic memory in diabetes. The basis for this metabolic memory was attributed to oxidative stress, chronic inflammation, non-enzymatic glycation of proteins and importantly, epigenetic changes. This highlights the importance of linking new therapeutics targeting epigenetic mechanisms with traditional antidiabetic drugs.

Conclusion: Although new data is evolving on the relation between DNA methylation, protein misfolding, and the etiology of diabetes, more studies are required for developing new relevant diagnostics and therapeutics.

Keywords: Diabetes, DNA methylation, protein folding, diet, aging, obesity.

Graphical Abstract
Roden, M. Diabetes mellitus: definition, classification and diagnosis. Wien. Klin. Wochenschr., 2016, 128(Suppl. 2), S37-S40.
[] [PMID: 27052219]
You, W.P.; Henneberg, M. Type 1 diabetes prevalence increasing globally and regionally: the role of natural selection and life expectancy at birth. BMJ Open Diabetes Res. Care, 2016, 4(1)e000161
[] [PMID: 26977306]
Bird, A. Perceptions of epigenetics. Nature, 2007, 447(7143), 396-398.
[] [PMID: 17522671]
Bird, A. On the track of DNA methylation: An interview with Adrian Bird by Jane Gitschier. PLoS Genet., 2009, 5(10)e1000667
[] [PMID: 19834538]
Bansal, A.; Simmons, R.A. Epigenetics and developmental origins of diabetes: correlation or causation? Am. J. Physiol. Endocrinol. Metab., 2018, 315(1), E15-E28.
[] [PMID: 29406781]
Jerram, S.T.; Dang, M.N.; Leslie, R.D. The Role of Epigenetics in Type 1 Diabetes. Curr. Diab. Rep., 2017, 17(10), 89.
[] [PMID: 28815391]
Bird, A. DNA methylation patterns and epigenetic memory. Genes Dev., 2002, 16(1), 6-21.
[] [PMID: 11782440]
Edwards, J.R.; O’Donnell, A.H.; Rollins, R.A.; Peckham, H.E.; Lee, C.; Milekic, M.H.; Chanrion, B.; Fu, Y.; Su, T.; Hibshoosh, H.; Gingrich, J.A.; Haghighi, F.; Nutter, R.; Bestor, T.H. Chromatin and sequence features that define the fine and gross structure of genomic methylation patterns. Genome Res., 2010, 20(7), 972-980.
[] [PMID: 20488932]
Deaton, A.M.; Bird, A. CpG islands and the regulation of transcription. Genes Dev., 2011, 25(10), 1010-1022.
[] [PMID: 21576262]
Bird, A.P.; Wolffe, A.P. Methylation-induced repression--belts, braces, and chromatin. Cell, 1999, 99(5), 451-454.
[] [PMID: 10589672]
Michels, K.B.; Binder, A.M.; Dedeurwaerder, S.; Epstein, C.B.; Greally, J.M.; Gut, I.; Houseman, E.A.; Izzi, B.; Kelsey, K.T.; Meissner, A.; Milosavljevic, A.; Siegmund, K.D.; Bock, C.; Irizarry, R.A. Recommendations for the design and analysis of epigenome-wide association studies. Nat. Methods, 2013, 10(10), 949-955.
[] [PMID: 24076989]
Rakyan, V.K.; Down, T.A.; Balding, D.J.; Beck, S. Epigenome-wide association studies for common human diseases. Nat. Rev. Genet., 2011, 12(8), 529-541.
[] [PMID: 21747404]
Cheung, M.S.; Gasic, A.G. Towards developing principles of protein folding and dynamics in the cell. Phys. Biol., 2018, 15(6)063001
[] [PMID: 29939151]
Chen, E.; Tsai, T.H.; Li, L.; Saha, P.; Chan, L.; Chang, B.H. PLIN2 is a Key Regulator of the Unfolded Protein Response and Endoplasmic Reticulum Stress Resolution in Pancreatic β Cells. Sci. Rep., 2017, 7, 40855.
[] [PMID: 28102311]
Brozzi, F.; Eizirik, D.L. ER stress and the decline and fall of pancreatic beta cells in type 1 diabetes. Ups. J. Med. Sci., 2016, 121(2), 133-139.
[] [PMID: 26899404]
Engerman, R.L.; Kern, T.S. Progression of incipient diabetic retinopathy during good glycemic control. Diabetes, 1987, 36(7), 808-812.
[] [PMID: 3556280]
Testa, R.; Bonfigli, A.R.; Prattichizzo, F.; La Sala, L.; De Nigris, V.; Ceriello, A. The “Metabolic Memory” Theory and the Early Treatment of Hyperglycemia in Prevention of Diabetic Complications. Nutrients, 2017, 9(5)E437
[] [PMID: 28452927]
Reddy, M.A.; Zhang, E.; Natarajan, R. Epigenetic mechanisms in diabetic complications and metabolic memory. Diabetologia, 2015, 58(3), 443-455.
[] [PMID: 25481708]
Reddy, M.A.; Natarajan, R. Role of epigenetic mechanisms in the vascular complications of diabetes. Subcell. Biochem., 2013, 61, 435-454.
[] [PMID: 23150262]
Thompson, J.A.; Webb, R.C. Potential role of Toll-like receptors in programming of vascular dysfunction. Clin. Sci. (Lond.), 2013, 125(1), 19-25.
[] [PMID: 23485061]
Miao, F.; Gonzalo, I.G.; Lanting, L.; Natarajan, R. In vivo chromatin remodeling events leading to inflammatory gene transcription under diabetic conditions. J. Biol. Chem., 2004, 279(17), 18091-18097.
[] [PMID: 14976218]
Todd, J.A. Etiology of type 1 diabetes. Immunity, 2010, 32(4), 457-467.
[] [PMID: 20412756]
Knip, M.; Veijola, R.; Virtanen, S.M.; Hyöty, H.; Vaarala, O.; Akerblom, H.K. Environmental triggers and determinants of type 1 diabetes. Diabetes, 2005, 54(Suppl. 2), S125-S136.
[] [PMID: 16306330]
Leslie, R.D.; Delli Castelli, M. Age-dependent influences on the origins of autoimmune diabetes: evidence and implications. Diabetes, 2004, 53(12), 3033-3040.
[] [PMID: 15561931]
Redondo, M.J.; Yu, L.; Hawa, M.; Mackenzie, T.; Pyke, D.A.; Eisenbarth, G.S.; Leslie, R.D. Heterogeneity of type I diabetes: analysis of monozygotic twins in Great Britain and the United States. Diabetologia, 2001, 44(3), 354-362.
[] [PMID: 11317668]
Hyttinen, V.; Kaprio, J.; Kinnunen, L.; Koskenvuo, M.; Tuomilehto, J. Genetic liability of type 1 diabetes and the onset age among 22,650 young Finnish twin pairs: a nationwide follow-up study. Diabetes, 2003, 52(4), 1052-1055.
[] [PMID: 12663480]
Kim, E.; Kwak, S.H.; Chung, H.R.; Ohn, J.H.; Bae, J.H.; Choi, S.H.; Park, K.S.; Hong, J.S.; Sung, J.; Jang, H.C. DNA methylation profiles in sibling pairs discordant for intrauterine exposure to maternal gestational diabetes. Epigenetics, 2017, 12(10), 825-832.
[] [PMID: 29099273]
Williams, K.T.; Garrow, T.A.; Schalinske, K.L. Type I diabetes leads to tissue-specific DNA hypomethylation in male rats. J. Nutr., 2008, 138(11), 2064-2069.
[] [PMID: 18936199]
Morahan, G. Insights into type 1 diabetes provided by genetic analyses. Curr. Opin. Endocrinol. Diabetes Obes., 2012, 19(4), 263-270.
[] [PMID: 22732486]
Shield, J.P.; Gardner, R.J.; Wadsworth, E.J.; Whiteford, M.L.; James, R.S.; Robinson, D.O.; Baum, J.D.; Temple, I.K. Aetiopathology and genetic basis of neonatal diabetes. Arch. Dis. Child. Fetal Neonatal Ed., 1997, 76(1), F39-F42.
[] [PMID: 9059185]
Shield, J.P.; Baum, J.D. Is transient neonatal diabetes a risk factor for diabetes in later life? Lancet, 1993, 341(8846), 693.
[] [PMID: 8095597]
Yamazaki, M.; Sugie, H.; Oguma, M.; Yorifuji, T.; Tajima, T.; Yamagata, T. Sulfonylurea treatment in an infant with transient neonatal diabetes mellitus caused by an adenosine triphosphate binding cassette subfamily C member 8 gene mutation. Clin. Pediatr. Endocrinol., 2017, 26(3), 165-169.
[] [PMID: 28804207]
Mackay, D.; Bens, S.; Perez de Nanclares, G.; Siebert, R.; Temple, I.K. Clinical utility gene card for: Transient Neonatal Diabetes Mellitus, 6q24-related. Eur. J. Hum. Genet., 2014, 22(9)
[] [PMID: 24569603]
Li, X.; Ito, M.; Zhou, F.; Youngson, N.; Zuo, X.; Leder, P.; Ferguson-Smith, A.C. A maternal-zygotic effect gene, Zfp57, maintains both maternal and paternal imprints. Dev. Cell, 2008, 15(4), 547-557.
[] [PMID: 18854139]
Quenneville, S.; Verde, G.; Corsinotti, A.; Kapopoulou, A.; Jakobsson, J.; Offner, S.; Baglivo, I.; Pedone, P.V.; Grimaldi, G.; Riccio, A.; Trono, D. In embryonic stem cells, ZFP57/KAP1 recognize a methylated hexanucleotide to affect chromatin and DNA methylation of imprinting control regions. Mol. Cell, 2011, 44(3), 361-372.
[] [PMID: 22055183]
Fradin, D.; Le Fur, S.; Mille, C.; Naoui, N.; Groves, C.; Zelenika, D.; McCarthy, M.I.; Lathrop, M.; Bougnères, P. Association of the CpG methylation pattern of the proximal insulin gene promoter with type 1 diabetes. PLoS One, 2012, 7(5)e36278
[] [PMID: 22567146]
Rakyan, V.K.; Beyan, H.; Down, T.A.; Hawa, M.I.; Maslau, S.; Aden, D.; Daunay, A.; Busato, F.; Mein, C.A.; Manfras, B.; Dias, K.R.; Bell, C.G.; Tost, J.; Boehm, B.O.; Beck, S.; Leslie, R.D. Identification of type 1 diabetes-associated DNA methylation variable positions that precede disease diagnosis. PLoS Genet., 2011, 7(9)e1002300
[] [PMID: 21980303]
Inadera, H. Developmental origins of obesity and type 2 diabetes: molecular aspects and role of chemicals. Environ. Health Prev. Med., 2013, 18(3), 185-197.
[] [PMID: 23382021]
Salbaum, J.M.; Kappen, C. Responses of the embryonic epigenome to maternal diabetes. Birth Defects Res. A Clin. Mol. Teratol., 2012, 94(10), 770-781.
[] [PMID: 22786762]
Desiderio, A.; Spinelli, R.; Ciccarelli, M.; Nigro, C.; Miele, C.; Beguinot, F.; Raciti, G.A. Epigenetics: spotlight on type 2 diabetes and obesity. J. Endocrinol. Invest., 2016, 39(10), 1095-1103.
[] [PMID: 27180180]
Puigserver, P.; Spiegelman, B.M. Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator. Endocr. Rev., 2003, 24(1), 78-90.
[] [PMID: 12588810]
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(4), 615-622.
[] [PMID: 18270681]
Rönn, T.; Poulsen, P.; Hansson, O.; Holmkvist, J.; Almgren, P.; Nilsson, P.; Tuomi, T.; Isomaa, B.; Groop, L.; Vaag, A.; Ling, C. Age influences DNA methylation and gene expression of COX7A1 in human skeletal muscle. Diabetologia, 2008, 51(7), 1159-1168.
[] [PMID: 18488190]
Mootha, V.K.; Lindgren, C.M.; Eriksson, K.F.; Subramanian, A.; Sihag, S.; Lehar, J.; Puigserver, P.; Carlsson, E.; Ridderstråle, M.; Laurila, E.; Houstis, N.; Daly, M.J.; Patterson, N.; Mesirov, J.P.; Golub, T.R.; Tamayo, P.; Spiegelman, B.; Lander, E.S.; Hirschhorn, J.N.; Altshuler, D.; Groop, L.C. PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat. Genet., 2003, 34(3), 267-273.
[] [PMID: 12808457]
Vaxillaire, M.; Froguel, P. Monogenic diabetes in the young, pharmacogenetics and relevance to multifactorial forms of type 2 diabetes. Endocr. Rev., 2008, 29(3), 254-264.
[] [PMID: 18436708]
Caro, J.F.; Triester, S.; Patel, V.K.; Tapscott, E.B.; Frazier, N.L.; Dohm, G.L. Liver glucokinase: decreased activity in patients with type II diabetes. Horm. Metab. Res., 1995, 27(1), 19-22.
[] [PMID: 7729787]
Jiang, M.H.; Fei, J.; Lan, M.S.; Lu, Z.P.; Liu, M.; Fan, W.W.; Gao, X.; Lu, D.R. Hypermethylation of hepatic Gck promoter in ageing rats contributes to diabetogenic potential. Diabetologia, 2008, 51(8), 1525-1533.
[] [PMID: 18496667]
de Mello, V.D.; Pulkkinen, L.; Lalli, M.; Kolehmainen, M.; Pihlajamäki, J.; Uusitupa, M. DNA methylation in obesity and type 2 diabetes. Ann. Med., 2014, 46(3), 103-113.
[] [PMID: 24779963]
Milagro, F.I.; Campión, J.; García-Díaz, D.F.; Goyenechea, E.; Paternain, L.; Martínez, J.A. High fat diet-induced obesity modifies the methylation pattern of leptin promoter in rats. J. Physiol. Biochem., 2009, 65(1), 1-9.
[] [PMID: 19588726]
Melzner, I.; Scott, V.; Dorsch, K.; Fischer, P.; Wabitsch, M.; Brüderlein, S.; Hasel, C.; Möller, P. Leptin gene expression in human preadipocytes is switched on by maturation-induced demethylation of distinct CpGs in its proximal promoter. J. Biol. Chem., 2002, 277(47), 45420-45427.
[] [PMID: 12213831]
Yokomori, N.; Tawata, M.; Onaya, T. DNA demethylation modulates mouse leptin promoter activity during the differentiation of 3T3-L1 cells. Diabetologia, 2002, 45(1), 140-148.
[] [PMID: 11845234]
Taylor, P.D.; McConnell, J.; Khan, I.Y.; Holemans, K.; Lawrence, K.M.; Asare-Anane, H.; Persaud, S.J.; Jones, P.M.; Petrie, L.; Hanson, M.A.; Poston, L. Impaired glucose homeostasis and mitochondrial abnormalities in offspring of rats fed a fat-rich diet in pregnancy. Am. J. Physiol. Regul. Integr. Comp. Physiol., 2005, 288(1), R134-R139.
[] [PMID: 15388492]
Khan, I.Y.; Dekou, V.; Douglas, G.; Jensen, R.; Hanson, M.A.; Poston, L.; Taylor, P.D. A high-fat diet during rat pregnancy or suckling induces cardiovascular dysfunction in adult offspring. Am. J. Physiol. Regul. Integr. Comp. Physiol., 2005, 288(1), R127-R133.
[] [PMID: 15308487]
Duhl, D.M.; Vrieling, H.; Miller, K.A.; Wolff, G.L.; Barsh, G.S. Neomorphic agouti mutations in obese yellow mice. Nat. Genet., 1994, 8(1), 59-65.
[] [PMID: 7987393]
Lobanenkov, V.; Loukinov, D.; Pugacheva, E. Environmental epigenomics and disease susceptibility. Keystone symposia on molecular and cellular biology. The Grove Park Hotel & Spa, Ashville, NC, USA, 27 March–1 April 2011. Epigenomics, 2011, 3(3), 261-266.
[] [PMID: 22122336]
Wolff, G.L.; Roberts, D.W.; Mountjoy, K.G. Physiological consequences of ectopic agouti gene expression: the yellow obese mouse syndrome. Physiol. Genomics, 1999, 1(3), 151-163.
[] [PMID: 11015573]
Lumey, L.H.; Stein, A.D.; Kahn, H.S.; van der Pal-de Bruin, K.M.; Blauw, G.J.; Zybert, P.A.; Susser, E.S. Cohort profile: the Dutch Hunger Winter families study. Int. J. Epidemiol., 2007, 36(6), 1196-1204.
[] [PMID: 17591638]
van der Meulen, J. Glucose tolerance in adults after prenatal exposure to famine. Lancet, 2001, 357(9270), 1797-1798.
[] [PMID: 11407377]
Heijmans, B.T.; Tobi, E.W.; Stein, A.D.; Putter, H.; Blauw, G.J.; Susser, E.S.; Slagboom, P.E.; Lumey, L.H. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc. Natl. Acad. Sci. USA, 2008, 105(44), 17046-17049.
[] [PMID: 18955703]
El Hajj, N.; Pliushch, G.; Schneider, E.; Dittrich, M.; Müller, T.; Korenkov, M.; Aretz, M.; Zechner, U.; Lehnen, H.; Haaf, T. Metabolic programming of MEST DNA methylation by intrauterine exposure to gestational diabetes mellitus. Diabetes, 2013, 62(4), 1320-1328.
[] [PMID: 23209187]
Takahashi, M.; Kamei, Y.; Ezaki, O. Mest/Peg1 imprinted gene enlarges adipocytes and is a marker of adipocyte size. Am. J. Physiol. Endocrinol. Metab., 2005, 288(1), E117-E124.
[] [PMID: 15353408]
Ge, Z.J.; Liang, Q.X.; Hou, Y.; Han, Z.M.; Schatten, H.; Sun, Q.Y.; Zhang, C.L. Maternal obesity and diabetes may cause DNA methylation alteration in the spermatozoa of offspring in mice. Reprod. Biol. Endocrinol., 2014, 12, 29.
[] [PMID: 24721882]
Crujeiras, A. B.; Diaz-Lagares, A.; Moreno-Navarrete, J. M.; Sandoval, J.; Hervas, D.; Gomez, A.; Ricart, W.; Casanueva, F. F.; Esteller, M.; Fernandez-Real, J. M. Genome-wide DNA methylation pattern in visceral adipose tissue differentiates insulin-resistant from insulin-sensitive obese subjects., 2016.
Rodríguez-Rodero, S.; Menéndez-Torre, E.; Fernández-Bayón, G.; Morales-Sánchez, P.; Sanz, L.; Turienzo, E.; González, J.J.; Martinez-Faedo, C.; Suarez-Gutiérrez, L.; Ares, J.; Díaz-Naya, L.; Martin-Nieto, A.; Fernández-Morera, J.L.; Fraga, M.F.; Delgado-Álvarez, E. Altered intragenic DNA methylation of HOOK2 gene in adipose tissue from individuals with obesity and type 2 diabetes. PLoS One, 2017, 12(12)e0189153
[] [PMID: 29228058]
Fahey, T.J., III; Sadaty, A.; Jones, W.G., II; Barber, A.; Smoller, B.; Shires, G.T. Diabetes impairs the late inflammatory response to wound healing. J. Surg. Res., 1991, 50(4), 308-313.
[] [PMID: 2020184]
Yan, J.; Tie, G.; Wang, S.; Tutto, A.; DeMarco, N.; Khair, L.; Fazzio, T.G.; Messina, L.M. Diabetes impairs wound healing by Dnmt1-dependent dysregulation of hematopoietic stem cells differentiation towards macrophages. Nat. Commun., 2018, 9(1), 33.
[] [PMID: 29295997]
Chen, G.; Chen, J.; Yan, Z.; Li, Z.; Yu, M.; Guo, W.; Tian, W. Maternal diabetes modulates dental epithelial stem cells proliferation and self-renewal in offspring through apurinic/apyrimidini-cendonuclease 1-mediated DNA methylation. Sci. Rep., 2017, 7, 40762.
[] [PMID: 28094306]
Akirav, E.M.; Lebastchi, J.; Galvan, E.M.; Henegariu, O.; Akirav, M.; Ablamunits, V.; Lizardi, P.M.; Herold, K.C. Detection of β cell death in diabetes using differentially methylated circulating DNA. Proc. Natl. Acad. Sci. USA, 2011, 108(47), 19018-19023.
[] [PMID: 22074781]
Toperoff, G.; Aran, D.; Kark, J.D.; Rosenberg, M.; Dubnikov, T.; Nissan, B.; Wainstein, J.; Friedlander, Y.; Levy-Lahad, E.; Glaser, B.; Hellman, A. Genome-wide survey reveals predisposing diabetes type 2-related DNA methylation variations in human peripheral blood. Hum. Mol. Genet., 2012, 21(2), 371-383.
[] [PMID: 21994764]
Fawcett, K.A.; Barroso, I. The genetics of obesity: FTO leads the way. Trends Genet., 2010, 26(6), 266-274.
[] [PMID: 20381893]
van Otterdijk, S.D.; Binder, A.M.; Szarc Vel Szic, K.; Schwald, J.; Michels, K.B. DNA methylation of candidate genes in peripheral blood from patients with type 2 diabetes or the metabolic syndrome. PLoS One, 2017, 12(7)e0180955
[] [PMID: 28727822]
Gong, L.; Goswami, S.; Giacomini, K.M.; Altman, R.B.; Klein, T.E. Metformin pathways: pharmacokinetics and pharmacodynamics. Pharmacogenet. Genomics, 2012, 22(11), 820-827.
[] [PMID: 22722338]
García-Calzón, S.; Perfilyev, A.; Männistö, V.; de Mello, V.D.; Nilsson, E.; Pihlajamäki, J.; Ling, C. Diabetes medication associates with DNA methylation of metformin transporter genes in the human liver. Clin. Epigenetics, 2017, 9, 102.
[] [PMID: 28947922]
Liang, L.; Chen, J.; Zhan, L.; Lu, X.; Sun, X.; Sui, H.; Zheng, L.; Xiang, H.; Zhang, F. Endoplasmic reticulum stress impairs insulin receptor signaling in the brains of obese rats. PLoS One, 2015, 10(5)e0126384
[] [PMID: 25978724]
Kimura, K.; Jin, H.; Ogawa, M.; Aoe, T. Dysfunction of the ER chaperone BiP accelerates the renal tubular injury. Biochem. Biophys. Res. Commun., 2008, 366(4), 1048-1053.
[] [PMID: 18158912]
Chang, J.H.; Gurley, S.B. Assessment of diabetic nephropathy in the Akita mouse. Methods Mol. Biol., 2012, 933, 17-29.
[] [PMID: 22893398]
Chen, C.M.; Wu, C.T.; Chiang, C.K.; Liao, B.W.; Liu, S.H. C/EBP homologous protein (CHOP) deficiency aggravates hippocampal cell apoptosis and impairs memory performance. PLoS One, 2012, 7(7)e40801
[] [PMID: 22815824]
Sundar Rajan, S.; Srinivasan, V.; Balasubramanyam, M.; Tatu, U. Endoplasmic reticulum (ER) stress & diabetes. Indian J. Med. Res., 2007, 125(3), 411-424.
[PMID: 17496365]
Hetz, C.; Glimcher, L.H. Fine-tuning of the unfolded protein response: Assembling the IRE1alpha interactome. Mol. Cell, 2009, 35(5), 551-561.
[] [PMID: 19748352]
Hetz, C. Bernasconi, P.; Fisher, J.; Lee, A. H.; Bassik, M. C.; Antonsson, B.; Brandt, G. S.; Iwakoshi, N. N.; Schinzel, A.; Glimcher, L. H.; Korsmeyer, S. J., Proapoptotic BAX and BAK modulate the unfolded protein response by a direct in-teraction with IRE1alpha. Science, 2006, 312(5773), 572-576.
[] [PMID: 16645094]
Zhi, W.; Sharma, A.; Purohit, S.; Miller, E.; Bode, B.; Ander-son, S. W.; Reed, J. C.; Steed, R. D.; Steed, L.; Hopkins, D.; She, J. X. Discovery and validation of serum protein changes in type 1 diabetes patients using high throughput two dimen-sional liquid chromatography-mass spectrometry and immu-noassays., 2011.
Hull, R.L.; Westermark, G.T.; Westermark, P.; Kahn, S.E. Islet amyloid: a critical entity in the pathogenesis of type 2 diabetes. J. Clin. Endocrinol. Metab., 2004, 89(8), 3629-3643.
[] [PMID: 15292279]
Volkmar, M.; Dedeurwaerder, S.; Cunha, D.A.; Ndlovu, M.N.; Defrance, M.; Deplus, R.; Calonne, E.; Volkmar, U.; Igoillo-Esteve, M.; Naamane, N.; Del Guerra, S.; Masini, M.; Bugliani, M.; Marchetti, P.; Cnop, M.; Eizirik, D.L.; Fuks, F. DNA methylation profiling identifies epigenetic dysregulation in pancreatic islets from type 2 diabetic patients. EMBO J., 2012, 31(6), 1405-1426.
[] [PMID: 22293752]
Sun, G.D.; Kobayashi, T.; Abe, M.; Tada, N.; Adachi, H.; Shiota, A.; Totsuka, Y.; Hino, O. The endoplasmic reticulum stress-inducible protein Niban regulates eIF2alpha and S6K1/4E-BP1 phosphorylation. Biochem. Biophys. Res. Commun., 2007, 360(1), 181-187.
[] [PMID: 17588536]
Mungrue, I.N.; Pagnon, J.; Kohannim, O.; Gargalovic, P.S.; Lusis, A.J. CHAC1/MGC4504 is a novel proapoptotic component of the unfolded protein response, downstream of the ATF4-ATF3-CHOP cascade. J. Immunol., 2009, 182(1), 466-476.
[] [PMID: 19109178]
Eizirik, D.L.; Cardozo, A.K.; Cnop, M. The role for endoplasmic reticulum stress in diabetes mellitus. Endocr. Rev., 2008, 29(1), 42-61.
[] [PMID: 18048764]
Palsamy, P.; Bidasee, K.R.; Ayaki, M.; Augusteyn, R.C.; Chan, J.Y.; Shinohara, T. Methylglyoxal induces endoplasmic reticulum stress and DNA demethylation in the Keap1 promoter of human lens epithelial cells and age-related cataracts. Free Radic. Biol. Med., 2014, 72, 134-148.
[] [PMID: 24746615]
Periyasamy, P.; Shinohara, T. Age-related cataracts: Role of unfolded protein response, Ca2+ mobilization, epigenetic DNA modifications, and loss of Nrf2/Keap1 dependent cytoprotection. Prog. Retin. Eye Res., 2017, 60, 1-19.
[] [PMID: 28864287]
Ma, Q. Role of nrf2 in oxidative stress and toxicity. Annu. Rev. Pharmacol. Toxicol., 2013, 53, 401-426.
[] [PMID: 23294312]
Moreau, K.L.; King, J.A. Protein misfolding and aggregation in cataract disease and prospects for prevention. Trends Mol. Med., 2012, 18(5), 273-282.
[] [PMID: 22520268]
Huang, Y.; Chavez, L.; Chang, X.; Wang, X.; Pastor, W.A.; Kang, J.; Zepeda-Martínez, J.A.; Pape, U.J.; Jacobsen, S.E.; Peters, B.; Rao, A. Distinct roles of the methylcytosine oxidases Tet1 and Tet2 in mouse embryonic stem cells. Proc. Natl. Acad. Sci. USA, 2014, 111(4), 1361-1366.
[] [PMID: 24474761]
Bansal, A.; Pinney, S.E. DNA methylation and its role in the pathogenesis of diabetes. Pediatr. Diabetes, 2017, 18(3), 167-177.
[] [PMID: 28401680]
Carol Man Gao, A.Y.Y.; Wang, X. Erika Magdangal, Cleo Salisbury, David Peretz, Ronald N. Zuckermann, Mi-chael D. Connolly, Oskar Hansson, Lennart Minthon, Henrik Zetterberg, Kaj Blennow, Joseph P. Fedynyshyn, Sophie Al-lauzen, Aβ40 Oligomers Identified as a Potential Biomarker for the Diagnosis of Alzheimer’s Disease. PLoS One, 2010.

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