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2000
Volume 25, Issue 8
  • ISSN: 1871-5303
  • E-ISSN: 2212-3873

Abstract

The rapidly emerging prevalence of type 2 diabetes mellitus (T2DM) and its associated complications have formed an increasingly serious threat to human life and health. Therefore, there is an urgent requirement to investigate the pathogenesis of T2DM and its complications, which will be conducive to discovering effective drugs for prevention and treatment. N6-methyladenosine (m6A) methylation is the most abundant and prevalent epigenetic modification of mRNA in mammals. m6A methylation is a dynamically reversible epigenetic transcriptome modification process that is jointly regulated by methyltransferases, demethylases and methylated reading proteins, which control the fate of target mRNAs through influencing splicing, translation and decay. Recent studies have revealed that m6A methylation plays an important role in β cellular function, insulin sensitivity and glycolipid metabolism. In this review, we summarized the current roles of m6A methylation in T2DM and T2DM-related complications such as diabetes nephropathy (DN), diabetes cardiovascular disease (DCD) and diabetes retinopathy (DR). Additionally, we sought the potential mechanism of m6A in T2DM and related complications, which may provide a rationale and strategy for potential therapeutic targeting of T2DM and its complications.

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References

  1. FeinbergA.P. LevchenkoA. Epigenetics as a mediator of plasticity in cancer.Science20233796632eaaw383510.1126/science.aaw383536758093
    [Google Scholar]
  2. FeinbergA.P. The key role of epigenetics in human disease prevention and mitigation.N. Engl. J. Med.2018378141323133410.1056/NEJMra140251329617578
    [Google Scholar]
  3. LaviU. Fernandez-MufiozR. DarnellJ.E.Jr Content of N-6 methyl adenylic acid in heterogeneous nuclear and messenger RNA of HeLa cells.Nucleic Acids Res.197741636910.1093/nar/4.1.63866178
    [Google Scholar]
  4. TanakaT. WeisblumB. Systematic difference in the methylation of ribosomal ribonucleic acid from gram-positive and gram-negative bacteria.J. Bacteriol.1975123277177410.1128/jb.123.2.771‑774.1975807565
    [Google Scholar]
  5. JiangX. LiuB. NieZ. DuanL. XiongQ. JinZ. YangC. ChenY. The role of m6A modification in the biological functions and diseases.Signal Transduct. Target. Ther.202161749110.1038/s41392‑020‑00450‑x33611339
    [Google Scholar]
  6. ZhengG. DahlJ.A. NiuY. FedorcsakP. HuangC.M. LiC.J. VågbøC.B. ShiY. WangW.L. SongS.H. LuZ. BosmansR.P.G. DaiQ. HaoY.J. YangX. ZhaoW.M. TongW.M. WangX.J. BogdanF. FuruK. FuY. JiaG. ZhaoX. LiuJ. KrokanH.E. KlunglandA. YangY.G. HeC. ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility.Mol. Cell2013491182910.1016/j.molcel.2012.10.01523177736
    [Google Scholar]
  7. GerkenT. GirardC.A. TungY.C.L. WebbyC.J. SaudekV. HewitsonK.S. YeoG.S.H. McDonoughM.A. CunliffeS. McNeillL.A. GalvanovskisJ. RorsmanP. RobinsP. PrieurX. CollA.P. MaM. JovanovicZ. FarooqiI.S. SedgwickB. BarrosoI. LindahlT. PontingC.P. AshcroftF.M. O’RahillyS. SchofieldC.J. The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase.Science200731858551469147210.1126/science.115171017991826
    [Google Scholar]
  8. YangY. HsuP.J. ChenY.S. YangY.G. Dynamic transcriptomic m6A decoration: writers, erasers, readers and functions in RNA metabolism.Cell Res.201828661662410.1038/s41422‑018‑0040‑829789545
    [Google Scholar]
  9. HsuP.J. ZhuY.F. MaH.H. GuoY.H. ShuX.D. LiuY.Y. QiM HsuP.J. ZhuY. MaH. GuoY. ShiX. LiuY. QiM. LuZ. ShiH. WangJ. ChengY. LuoG. DaiQ. LiuM. GuoX. ShaJ. ShenB. HeC. Ythdc2 is an N6-methyladenosine binding protein that regulates mammalian spermatogenesis.Cell Res.20172791115112710.1038/cr.2017.9928809393
    [Google Scholar]
  10. IvanovaI. MuchC. Di GiacomoM. AzziC. MorganM. MoreiraP.N. MonahanJ. CarrieriC. EnrightA.J. O’CarrollD. The RNA m 6 A reader YTHDF2 is essential for the post-transcriptional regulation of the maternal transcriptome and oocyte Competence.Mol. Cell201767610591067.e410.1016/j.molcel.2017.08.00328867294
    [Google Scholar]
  11. LiA. ChenY.S. PingX.L. YangX. XiaoW. YangY. SunH.Y. ZhuQ. BaidyaP. WangX. BhattaraiD.P. ZhaoY.L. SunB.F. YangY.G. Cytoplasmic m6A reader YTHDF3 promotes mRNA translation.Cell Res.201727344444710.1038/cr.2017.1028106076
    [Google Scholar]
  12. ZhaoX. YangY. SunB.F. ZhaoY.L. YangY.G. FTO and obesity: mechanisms of association.Curr. Diab. Rep.201414548649510.1007/s11892‑014‑0486‑024627050
    [Google Scholar]
  13. SunT. WuR. MingL. The role of m6A RNA methylation in cancer.Biomed. Pharmacother.201911210861310.1016/j.biopha.2019.10861330784918
    [Google Scholar]
  14. SunH. SaeediP. KarurangaS. PinkepankM. OgurtsovaK. DuncanB.B. SteinC. BasitA. ChanJ.C.N. MbanyaJ.C. PavkovM.E. RamachandaranA. WildS.H. JamesS. HermanW.H. ZhangP. BommerC. KuoS. BoykoE.J. MaglianoD.J. IDF diabetes atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045.Diabetes Res. Clin. Pract.20221835110911910.1016/j.diabres.2021.10911934879977
    [Google Scholar]
  15. SagooM.K. GnudiL. Diabetic nephropathy: An overview.Methods Mol. Biol.20202067123710.1007/978‑1‑4939‑9841‑8_131701441
    [Google Scholar]
  16. GlovaciD. FanW. WongN.D. Epidemiology of diabetes mellitus and cardiovascular disease.Curr. Cardiol. Rep.2019214212910.1007/s11886‑019‑1107‑y30828746
    [Google Scholar]
  17. TanT.E. WongT.Y. Diabetic retinopathy: Looking forward to 2030.Front. Endocrinol. (Lausanne)20231334107766910.3389/fendo.2022.107766936699020
    [Google Scholar]
  18. UnnikrishnanR. AnjanaR.M. MohanV. Diabetes mellitus and its complications in India.Nat. Rev. Endocrinol.201612635737010.1038/nrendo.2016.5327080137
    [Google Scholar]
  19. XinY. KimJ. OkamotoH. NiM. WeiY. AdlerC. MurphyA.J. YancopoulosG.D. LinC. GromadaJ. RNA sequencing of single human islet cells reveals type 2 diabetes genes.Cell Metab.201624460861510.1016/j.cmet.2016.08.01827667665
    [Google Scholar]
  20. De JesusD.F. ZhangZ. KahramanS. BrownN.K. ChenM. HuJ. GuptaM.K. HeC. KulkarniR.N. m6A mRNA methylation regulates human β-cell biology in physiological states and in type 2 diabetes.Nat. Metab.20191876577410.1038/s42255‑019‑0089‑931867565
    [Google Scholar]
  21. LiM. DengL. XuG. METTL14 promotes glomerular endothelial cell injury and diabetic nephropathy via m6A modification of α-klotho.Mol. Med.202127110611910.1186/s10020‑021‑00365‑534503454
    [Google Scholar]
  22. QiY. YaoR. ZhangW. CuiQ. KAT1 triggers YTHDF2-mediated ITGB1 mRNA instability to alleviate the progression of diabetic retinopathy.Pharmacol. Res.2021170710571310.1016/j.phrs.2021.10571334098071
    [Google Scholar]
  23. MengL. LinH. HuangX. WengJ. PengF. WuS. METTL14 suppresses pyroptosis and diabetic cardiomyopathy by downregulating TINCR lncRNA.Cell Death Dis.2022131385310.1038/s41419‑021‑04484‑z35013106
    [Google Scholar]
  24. KanL. GrozhikA.V. VedanayagamJ. PatilD.P. PangN. LimK.S. HuangY.C. JosephB. LinC.J. DespicV. GuoJ. YanD. KondoS. DengW.M. DedonP.C. JaffreyS.R. LaiE.C. The m6A pathway facilitates sex determination in Drosophila.Nat. Commun.2017811573710.1038/ncomms1573728675155
    [Google Scholar]
  25. FisherA.J. BealP.A. Structural basis for eukaryotic mRNA modification.Curr. Opin. Struct. Biol.20185321596810.1016/j.sbi.2018.05.00329913347
    [Google Scholar]
  26. WangP. DoxtaderK.A. NamY. Structural basis for cooperative function of mettl3 and mettl14 methyltransferases.Mol. Cell201663230631710.1016/j.molcel.2016.05.04127373337
    [Google Scholar]
  27. HuangH. WengH. ZhouK. WuT. ZhaoB.S. SunM. ChenZ. DengX. XiaoG. AuerF. KlemmL. WuH. ZuoZ. QinX. DongY. ZhouY. QinH. TaoS. DuJ. LiuJ. LuZ. YinH. MesquitaA. YuanC.L. HuY.C. SunW. SuR. DongL. ShenC. LiC. QingY. JiangX. WuX. SunM. GuanJ.L. QuL. WeiM. MüschenM. HuangG. HeC. YangJ. ChenJ. Histone H3 trimethylation at lysine 36 guides m6A RNA modification co-transcriptionally.Nature2019567774841441910.1038/s41586‑019‑1016‑730867593
    [Google Scholar]
  28. SatterwhiteE.R. MansfieldK.D. RNA methyltransferase METTL16 : Targets and function.Wiley Interdiscip. Rev. RNA2022132e168110.1002/wrna.168134227247
    [Google Scholar]
  29. LiuJ. YueY. HanD. WangX. FuY. ZhangL. JiaG. YuM. LuZ. DengX. DaiQ. ChenW. HeC. A METTL3–METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation.Nat. Chem. Biol.2014102939510.1038/nchembio.143224316715
    [Google Scholar]
  30. PingX.L. SunB.F. WangL. XiaoW. YangX. WangW.J. AdhikariS. ShiY. LvY. ChenY.S. ZhaoX. LiA. YangY. DahalU. LouX.M. LiuX. HuangJ. YuanW.P. ZhuX.F. ChengT. ZhaoY.L. WangX. DanielsenJ.M.R. LiuF. YangY.G. Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine methyltransferase.Cell Res.201424217718910.1038/cr.2014.324407421
    [Google Scholar]
  31. YueY. LiuJ. CuiX. CaoJ. LuoG. ZhangZ. ChengT. GaoM. ShuX. MaH. WangF. WangX. ShenB. WangY. FengX. HeC. LiuJ. VIRMA mediates preferential m6A mRNA methylation in 3′UTR and near stop codon and associates with alternative polyadenylation.Cell Discov.201841101810.1038/s41421‑018‑0019‑029507755
    [Google Scholar]
  32. SchwartzS. MumbachM.R. JovanovicM. WangT. MaciagK. BushkinG.G. MertinsP. Ter-OvanesyanD. HabibN. CacchiarelliD. SanjanaN.E. FreinkmanE. PacoldM.E. SatijaR. MikkelsenT.S. HacohenN. ZhangF. CarrS.A. LanderE.S. RegevA. Perturbation of m6A writers reveals two distinct classes of mRNA methylation at internal and 5′ sites.Cell Rep.20148128429610.1016/j.celrep.2014.05.04824981863
    [Google Scholar]
  33. KnucklesP. LenceT. HaussmannI.U. JacobD. KreimN. CarlS.H. MasielloI. HaresT. VillaseñorR. HessD. Andrade-NavarroM.A. BiggiogeraM. HelmM. SollerM. BühlerM. RoignantJ.Y. Zc3h13/Flacc is required for adenosine methylation by bridging the mRNA-binding factor Rbm15/Spenito to the m 6 A machinery component Wtap/Fl(2)d.Genes Dev.2018325-641542910.1101/gad.309146.11729535189
    [Google Scholar]
  34. PatilD.P. ChenC.K. PickeringB.F. ChowA. JacksonC. GuttmanM. JaffreyS.R. m6A RNA methylation promotes XIST-mediated transcriptional repression.Nature2016537762036937310.1038/nature1934227602518
    [Google Scholar]
  35. ZhaoB.S. RoundtreeI.A. HeC. Post-transcriptional gene regulation by mRNA modifications.Nat. Rev. Mol. Cell Biol.2017181314210.1038/nrm.2016.13227808276
    [Google Scholar]
  36. JiaG. YangC.G. YangS. JianX. YiC. ZhouZ. HeC. Oxidative demethylation of 3-methylthymine and 3-methyluracil in single-stranded DNA and RNA by mouse and human FTO.FEBS Lett.200858223-243313331910.1016/j.febslet.2008.08.01918775698
    [Google Scholar]
  37. JiaG. FuY. ZhaoX. DaiQ. ZhengG. YangY. YiC. LindahlT. PanT. YangY.G. HeC. N6-Methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO.Nat. Chem. Biol.201171288588710.1038/nchembio.68722002720
    [Google Scholar]
  38. LiuJ. JiaG. Methylation modifications in eukaryotic messenger RNA.J. Genet. Genomics2014411213310.1016/j.jgg.2013.10.00224480744
    [Google Scholar]
  39. MauerJ. LuoX. BlanjoieA. JiaoX. GrozhikA.V. PatilD.P. LinderB. PickeringB.F. VasseurJ.J. ChenQ. GrossS.S. ElementoO. DebartF. KiledjianM. JaffreyS.R. Reversible methylation of m6Am in the 5′ cap controls mRNA stability.Nature2017541763737137510.1038/nature2102228002401
    [Google Scholar]
  40. ChenW. ZhangL. ZhengG. FuY. JiQ. LiuF. ChenH. HeC. Crystal structure of the RNA demethylase ALKBH5 from zebrafish.FEBS Lett.2014588689289810.1016/j.febslet.2014.02.02124561204
    [Google Scholar]
  41. WangX. ZhaoB.S. RoundtreeI.A. LuZ. HanD. MaH. WengX. ChenK. ShiH. HeC. N6-methyladenosine modulates messenger rna translation efficiency.Cell201516161388139910.1016/j.cell.2015.05.01426046440
    [Google Scholar]
  42. LiuN. ZhouK.I. ParisienM. DaiQ. DiatchenkoL. PanT. N 6-methyladenosine alters RNA structure to regulate binding of a low-complexity protein.Nucleic Acids Res.201745106051606310.1093/nar/gkx14128334903
    [Google Scholar]
  43. LiuT. WeiQ. JinJ. LuoQ. LiuY. YangY. ChengC. LiL. PiJ. SiY. XiaoH. LiL. RaoS. WangF. YuJ. YuJ. ZouD. YiP. The m6A reader YTHDF1 promotes ovarian cancer progression via augmenting EIF3C translation.Nucleic Acids Res.20204873816383110.1093/nar/gkaa04831996915
    [Google Scholar]
  44. RoundtreeI.A. LuoG.Z. ZhangZ. WangX. ZhouT. CuiY. ShaJ. HuangX. GuerreroL. XieP. HeE. ShenB. HeC. YTHDC1 mediates nuclear export of N6-methyladenosine methylated mRNAs.eLife2017614e3131110.7554/eLife.3131128984244
    [Google Scholar]
  45. DuH. ZhaoY. HeJ. ZhangY. XiH. LiuM. MaJ. WuL. YTHDF2 destabilizes m(6)A-containing RNA through direct recruitment of the CCR4-NOT deadenylase complex.Nat Commun.201671262610.1038/ncomms12626
    [Google Scholar]
  46. MeyerK.D. PatilD.P. ZhouJ. ZinovievA. SkabkinM.A. ElementoO. PestovaT.V. QianS.B. JaffreyS.R. 5′ UTR m6A promotes cap-independent translation.Cell20151634999101010.1016/j.cell.2015.10.01226593424
    [Google Scholar]
  47. ShiH. WangX. LuZ. ZhaoB.S. MaH. HsuP.J. LiuC. HeC. YTHDF3 facilitates translation and decay of N6-methyladenosine-modified RNA.Cell Res.201727331532810.1038/cr.2017.1528106072
    [Google Scholar]
  48. AlarcónC.R. GoodarziH. LeeH. LiuX. TavazoieS. TavazoieS.F. HNRNPA2B1 Is a mediator of m6a-dependent nuclear rna processing events.Cell201516261299130810.1016/j.cell.2015.08.01126321680
    [Google Scholar]
  49. SamuelV.T. ShulmanG.I. Mechanisms for insulin resistance: common threads and missing links.Cell2012148585287110.1016/j.cell.2012.02.01722385956
    [Google Scholar]
  50. OgiharaT. MirmiraR.G. An islet in distress: β cell failure in type 2 diabetes.J. Diabetes Investig.20101412313310.1111/j.2040‑1124.2010.00021.x24843420
    [Google Scholar]
  51. WuS. WangL. HeY. ShiF. ZhuangH. MeiL. QianY. Effects of different mind-body exercises on glucose and lipid metabolism in patients with type 2 diabetes: A network meta-analysis.Complement. Ther. Clin. Pract.2023538410180210.1016/j.ctcp.2023.10180237769432
    [Google Scholar]
  52. HalimM. HalimA. The effects of inflammation, aging and oxidative stress on the pathogenesis of diabetes mellitus (type 2 diabetes).Diabetes Metab. Syndr.20191321165117210.1016/j.dsx.2019.01.04031336460
    [Google Scholar]
  53. YaribeygiH. SathyapalanT. AtkinS.L. SahebkarA. Molecularmechanisms linking oxidative stress and diabetes mellitus.Oxid. Med. Cell. Longev.202020201211310.1155/2020/860921332215179
    [Google Scholar]
  54. Juan-MateuJ. BajewS. Miret-CuestaM. ÍñiguezL.P. Lopez-PascualA. BonnalS. AtlaG. Bonàs-GuarchS. FerrerJ. ValcárcelJ. IrimiaM. Pancreatic microexons regulate islet function and glucose homeostasis.Nat. Metab.20235221923610.1038/s42255‑022‑00734‑236759540
    [Google Scholar]
  55. LiX. JiangY. SunX. WuY. ChenZ. METTL3 is required for maintaining β-cell function.Metabolism20211162115470210.1016/j.metabol.2021.15470233417895
    [Google Scholar]
  56. ChengY. YaoX.M. ZhouS.M. SunY. MengX.J. WangY. XingY.J. WanS.J. HuaQ. The m6A methyltransferase mettl3 ameliorates methylglyoxal-induced impairment of insulin secretion in pancreatic β cells by regulating mafa expression.Front. Endocrinol. (Lausanne)2022134291086810.3389/fendo.2022.91086835872977
    [Google Scholar]
  57. WangY. SunJ. LinZ. ZhangW. WangS. WangW. WangQ. NingG. m6A mRNA methylation controls functional maturation in neonatal murine β-cells.Diabetes20206981708172210.2337/db19‑090632404350
    [Google Scholar]
  58. TaneeraJ. PrasadR.B. DhaibanS. MohammedA.K. HaatajaL. ArvanP. HamadM. GroopL. WollheimC.B. Silencing of the FTO gene inhibits insulin secretion: An in vitro study using GRINCH cells.Mol. Cell. Endocrinol.201847237101710.1016/j.mce.2018.06.00329890211
    [Google Scholar]
  59. TaneeraJ. KhaliqueA. AbdrabhS. MohammedA.K. BouzidA. El-HuneidiW. BustanjiY. SulaimanN. AlbashaS. Saber-AyadM. HamadM. Fat mass and obesity-associated (FTO) gene is essential for insulin secretion and β-cell function: In vitro studies using INS-1 cells and human pancreatic islets.Life Sci.20243392412242110.1016/j.lfs.2024.12242138232799
    [Google Scholar]
  60. FanH.Q. HeW. XuK.F. WangZ.X. XuX.Y. ChenH. FTO inhibits insulin secretion and promotes nf-κb activation through positively regulating ros production in pancreatic β cells.PLoS One2015105e012770510.1371/journal.pone.012770526018652
    [Google Scholar]
  61. ReguéL. ZhaoL. JiF. WangH. AvruchJ. DaiN. RNA m6A reader IMP2/IGF2BP2 promotes pancreatic β-cell proliferation and insulin secretion by enhancing PDX1 expression.Mol. Metab.2021487210120910.1016/j.molmet.2021.10120933705986
    [Google Scholar]
  62. BailettiD. SentinelliF. PrudenteS. CiminiF.A. BarchettaI. TotaroM. Di CostanzoA. BarbonettiA. LeonettiF. CavalloM.G. BaroniM.G. Deep resequencing of 9 candidate genes identifies a role for ARAP1 and IGF2BP2 in modulating insulin secretion adjusted for insulin resistance in obese southern europeans.Int. J. Mol. Sci.20222331221123010.3390/ijms2303122135163144
    [Google Scholar]
  63. TahaparyD.L. PratisthitaL.B. FitriN.A. MarcellaC. WafaS. KurniawanF. RizkaA. TariganT.J.E. HarbuwonoD.S. PurnamasariD. SoewondoP. Challenges in the diagnosis of insulin resistance: Focusing on the role of HOMA-IR and Tryglyceride/glucose index.Diabetes Metab. Syndr.202216810258110.1016/j.dsx.2022.10258135939943
    [Google Scholar]
  64. XieW. MaL.L. XuY.Q. WangB.H. LiS.M. METTL3 inhibits hepatic insulin sensitivity via N6-methyladenosine modification of Fasn mRNA and promoting fatty acid metabolism.Biochem. Biophys. Res. Commun.2019518112012610.1016/j.bbrc.2019.08.01831405565
    [Google Scholar]
  65. LiY. ZhangQ. CuiG. ZhaoF. TianX. SunB.F. YangY. LiW. m6A Regulates liver metabolic disorders and hepatogenous diabetes.Genomics Proteomics Bioinformatics202018437138310.1016/j.gpb.2020.06.00333160098
    [Google Scholar]
  66. Saber-AyadM. ManzoorS. SerafiA.E. MahmoudI. HammoudehS. RaniA. AbusnanaS. SulaimanN. The FTO rs9939609 "A" allele is associated with impaired fasting glucose and insulin resistance in Emirati population.Gene2019681146939810.1016/j.gene.2018.09.053
    [Google Scholar]
  67. De LuisD.A. AllerR. IzaolaO. PrimoD. RomeroE. Association of the rs9939609 gene variant in FTO with insulin resistance, carciovascular risk factor and serum adipokine levels in obese patients.Nutr. Hosp.201633557358210.20960/nh.57327759977
    [Google Scholar]
  68. LuY. QieD. YangF. WuJ. LncRNA MEG3 aggravates adipocyte inflammation and insulin resistance by targeting IGF2BP2 to activate TLR4/NF-κB signaling pathway.Int. Immunopharmacol.20231215211046710.1016/j.intimp.2023.11046737348228
    [Google Scholar]
  69. LiX. AllayeeH. XiangA.H. TrigoE. HartialaJ. LawrenceJ.M. BuchananT.A. WatanabeR.M. Variation in IGF2BP2 interacts with adiposity to alter insulin sensitivity in Mexican Americans.Obesity (Silver Spring)200917472973610.1038/oby.2008.59319148120
    [Google Scholar]
  70. ReguéL. MinichielloL. AvruchJ. DaiN. Liver-specific deletion of IGF2 mRNA binding protein-2/IMP2 reduces hepatic fatty acid oxidation and increases hepatic triglyceride accumulation.J. Biol. Chem.201929431119441195110.1074/jbc.RA119.00877831209109
    [Google Scholar]
  71. PrasadM.K. MohandasS. RamkumarK.M. Dysfunctions, molecular mechanisms, and therapeutic strategies of pancreatic β- cells in diabetes.Apoptosis2023287-895897610.1007/s10495‑023‑01854‑037273039
    [Google Scholar]
  72. YangY. ShenF. HuangW. QinS. HuangJ.T. SergiC. YuanB.F. LiuS.M. Glucose is involved in the dynamic regulation of m6a in patients with type 2 diabetes.J. Clin. Endocrinol. Metab.2019104366567310.1210/jc.2018‑0061930137347
    [Google Scholar]
  73. BornaqueF. DelannoyC.P. CourtyE. RabhiN. CarneyC. RollandL. MorenoM. GromadaX. BourouhC. PetitP. DurandE. PattouF. Kerr-ConteJ. FroguelP. BonnefondA. OgerF. AnnicotteJ.S. Glucose regulates m6A methylation of RNA in pancreatic islets.Cells202211229130210.3390/cells1102029135053407
    [Google Scholar]
  74. LiuJ. LuoG. SunJ. MenL. YeH. HeC. RenD. METTL14 is essential for β-cell survival and insulin secretion.Biochim. Biophys. Acta Mol. Basis Dis.2019186592138214810.1016/j.bbadis.2019.04.01131029827
    [Google Scholar]
  75. PengS. XiaoW. JuD. SunB. HouN. LiuQ. WangY. ZhaoH. GaoC. ZhangS. CaoR. LiP. HuangH. MaY. WangY. LaiW. MaZ. ZhangW. HuangS. WangH. ZhangZ. ZhaoL. CaiT. ZhaoY.L. WangF. NieY. ZhiG. YangY.G. ZhangE.E. HuangN. Identification of entacapone as a chemical inhibitor of FTO mediating metabolic regulation through FOXO1.Sci. Transl. Med.201911488eaau711610.1126/scitranslmed.aau711630996080
    [Google Scholar]
  76. GaoL.P. ChenH.C. MaZ. ChenA.D. DuH.L. YinJ. JingY.H. Fibrillation of human islet amyloid polypeptide and its toxicity to pancreatic β-cells under lipid environment.Biochim. Biophys. Acta, Gen. Subj.20201864112942210.1016/j.bbagen.2019.12942231491457
    [Google Scholar]
  77. MoX. LeiS. ZhangY. ZhangH. Genome-wide enrichment of m6A-associated single-nucleotide polymorphisms in the lipid loci.Pharmacogenomics J.201919434735710.1038/s41397‑018‑0055‑z30262821
    [Google Scholar]
  78. YangY. CaiJ. YangX. WangK. SunK. YangZ. ZhangL. YangL. GuC. HuangX. WangZ. ZhuX. Dysregulated m6A modification promotes lipogenesis and development of non-alcoholic fatty liver disease and hepatocellular carcinoma.Mol. Ther.20223062342235310.1016/j.ymthe.2022.02.02135192934
    [Google Scholar]
  79. PawlakM. LefebvreP. StaelsB. Molecular mechanism of PPARα action and its impact on lipid metabolism, inflammation and fibrosis in non-alcoholic fatty liver disease.J. Hepatol.201562372073310.1016/j.jhep.2014.10.03925450203
    [Google Scholar]
  80. MizunoT.M. Fat mass and obesity associated (FTO) gene and hepatic glucose and lipid metabolism.Nutrients201810111600161210.3390/nu1011160030388740
    [Google Scholar]
  81. ZhouB. LiuC. XuL. YuanY. ZhaoJ. ZhaoW. ChenY. QiuJ. MengM. ZhengY. WangD. GaoX. LiX. ZhaoQ. WeiX. WuD. ZhangH. HuC. ZhuoX. ZhengM. WangH. LuY. MaX. N6-Methyladenosine reader protein YT521-B homology domain-containing 2 suppresses liver steatosis by regulation of mRNA stability of lipogenic genes.Hepatology20217319110310.1002/hep.3122032150756
    [Google Scholar]
  82. BigagliE. LodoviciM. Circulating oxidative stress biomarkers in clinical studies on type 2 diabetes and its complications.Oxid. Med. Cell. Longev.2019201911710.1155/2019/595368531214280
    [Google Scholar]
  83. Dalle-DonneI. RossiR. ColomboR. GiustariniD. MilzaniA. Biomarkers of oxidative damage in human disease.Clin. Chem.200652460162310.1373/clinchem.2005.06140816484333
    [Google Scholar]
  84. SergiD. BoulestinH. CampbellF.M. WilliamsL.M. The role of dietary advanced glycation end products in metabolic dysfunction.Mol. Nutr. Food Res.2021651190093410.1002/mnfr.20190093432246887
    [Google Scholar]
  85. HuangJ. YangF. LiuY. WangY. N6-methyladenosine RNA methylation in diabetic kidney disease.Biomed. Pharmacother.20241717311618510.1016/j.biopha.2024.11618538237350
    [Google Scholar]
  86. LuZ. LiuH. SongN. LiangY. ZhuJ. ChenJ. NingY. HuJ. FangY. TengJ. ZouJ. DaiY. DingX. METTL14 aggravates podocyte injury and glomerulopathy progression through N6-methyladenosine-dependent downregulating of Sirt1.Cell Death Dis.2021121088190210.1038/s41419‑021‑04156‑y34580283
    [Google Scholar]
  87. TangW. ZhaoY. ZhangH. PengY. RuiZ. METTL3 enhances NSD2 mRNA stability to reduce renal impairment and interstitial fibrosis in mice with diabetic nephropathy.BMC Nephrol.202223112413810.1186/s12882‑022‑02753‑335354439
    [Google Scholar]
  88. JiangL. LiuX. HuX. GaoL. ZengH. WangX. HuangY. ZhuW. WangJ. WenJ. MengX. WuY. METTL3-mediated m6A modification of TIMP2 mRNA promotes podocyte injury in diabetic nephropathy.Mol. Ther.20223041721174010.1016/j.ymthe.2022.01.00234995800
    [Google Scholar]
  89. LanJ. XuB. ShiX. PanQ. TaoQ. WTAP-mediated N6-methyladenosine modification of NLRP3 mRNA in kidney injury of diabetic nephropathy.Cell. Mol. Biol. Lett.2022271516410.1186/s11658‑022‑00350‑835761192
    [Google Scholar]
  90. LiauN.P.D. LaktyushinA. LucetI.S. MurphyJ.M. YaoS. WhitlockE. CallaghanK. NicolaN.A. KershawN.J. BabonJ.J. The molecular basis of JAK/STAT inhibition by SOCS1.Nat. Commun.2018911558156510.1038/s41467‑018‑04013‑129674694
    [Google Scholar]
  91. SunQ. GengH. ZhaoM. LiY. ChenX. ShaQ. LaiP. TangD. YangD. LiangJ. GuoM. FTO-mediated m 6 A modification of SOCS1 mRNA promotes the progression of diabetic kidney disease.Clin. Transl. Med.2022126e94210.1002/ctm2.94235731980
    [Google Scholar]
  92. MaC.X. MaX.N. GuanC.H. LiY.D. MauricioD. FuS.B. Cardiovascular disease in type 2 diabetes mellitus: progress toward personalized management.Cardiovasc. Diabetol.2022211748310.1186/s12933‑022‑01516‑635568946
    [Google Scholar]
  93. GuoM. YanR. JiQ. YaoH. SunM. DuanL. XueZ. JiaY. IFN regulatory Factor-1 induced macrophage pyroptosis by modulating m6A modification of circ_0029589 in patients with acute coronary syndrome.Int. Immunopharmacol.2020863810680010.1016/j.intimp.2020.10680032674051
    [Google Scholar]
  94. WeiX. YiX. LiuJ. SuiX. LiL. LiM. LvH. YiH. Circ-phkb promotes cell apoptosis and inflammation in LPS-induced alveolar macrophages via the TLR4/MyD88/NF-kB/CCL2 axis.Respir. Res.2024251627510.1186/s12931‑024‑02677‑638287405
    [Google Scholar]
  95. ZhengY. LiY. RanX. WangD. ZhengX. ZhangM. YuB. SunY. WuJ. Mettl14 mediates the inflammatory response of macrophages in atherosclerosis through the NF-κB/IL-6 signaling pathway.Cell. Mol. Life Sci.202279631132710.1007/s00018‑022‑04331‑035598196
    [Google Scholar]
  96. JianD. WangY. JianL. TangH. RaoL. ChenK. JiaZ. ZhangW. LiuY. ChenX. ShenX. GaoC. WangS. LiM. METTL14 aggravates endothelial inflammation and atherosclerosis by increasing FOXO1 N6-methyladeosine modifications.Theranostics202010208939895610.7150/thno.4517832802173
    [Google Scholar]
  97. JuW. LiuK. OuyangS. LiuZ. HeF. WuJ. Changes in N6-methyladenosine modification modulate diabetic cardiomyopathy by reducing myocardial fibrosis and myocyte hypertrophy.Front. Cell Dev. Biol.202192670257910.3389/fcell.2021.70257934368154
    [Google Scholar]
  98. ShaoY. LiM. YuQ. GongM. WangY. YangX. LiuL. LiuD. TanZ. ZhangY. QuY. LiH. WangY. JiaoL. ZhangY. CircRNA CDR1as promotes cardiomyocyte apoptosis through activating hippo signaling pathway in diabetic cardiomyopathy.Eur. J. Pharmacol.20229225217491510.1016/j.ejphar.2022.17491535339477
    [Google Scholar]
  99. YuanJ. LiuY. ZhouL. XueY. LuZ. GanJ. YTHDC2-Mediated circythdc2 n6-methyladenosine modification promotes vascular smooth muscle cells dysfunction through inhibiting ten-eleven translocation 2.Front. Cardiovasc. Med.202181368629310.3389/fcvm.2021.68629334660707
    [Google Scholar]
  100. ForresterJ.V. KuffovaL. DelibegovicM. The role of inflammation in diabetic retinopathy.Front. Immunol.2020116758368710.3389/fimmu.2020.58368733240272
    [Google Scholar]
  101. Luna-UlloaL.B. Hernández-MaquedaJ.G. Castañeda-PatlánM.C. Robles-FloresM. Protein kinase C in Wnt signaling: Implications in cancer initiation and progression.IUBMB Life2011631091592110.1002/iub.55921905203
    [Google Scholar]
  102. WinklerE.A. BellR.D. ZlokovicB.V. Pericyte-specific expression of PDGF beta receptor in mouse models with normal and deficient PDGF beta receptor signaling.Mol. Neurodegener.201051324110.1186/1750‑1326‑5‑3220738866
    [Google Scholar]
  103. SuoL. LiuC. ZhangQ.Y. YaoM.D. MaY. YaoJ. JiangQ. YanB. METTL3-mediated N 6 -methyladenosine modification governs pericyte dysfunction during diabetes-induced retinal vascular complication.Theranostics202212127728910.7150/thno.6344134987645
    [Google Scholar]
  104. ChenT. ZhuW. WangC. DongX. YuF. SuY. HuangJ. HuoL. WanP. ALKBH5-mediated m6A modification of a20 regulates microglia polarization in diabetic retinopathy.Front. Immunol.2022137181397910.3389/fimmu.2022.81397935300330
    [Google Scholar]
  105. ShanK. ZhouR. XiangJ. SunY. LiuC. LvM. XuJ. FTO regulates ocular angiogenesis via m6A-YTHDF2-dependent mechanism.Exp. Eye Res.20201974510810710.1016/j.exer.2020.10810732531187
    [Google Scholar]
  106. HuangC. QiP. CuiH. LuQ. GaoX. CircFAT1 regulates retinal pigment epithelial cell pyroptosis and autophagy via mediating m6A reader protein YTHDF2 expression in diabetic retinopathy.Exp. Eye Res.20222223710915210.1016/j.exer.2022.10915235714699
    [Google Scholar]
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