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pmid:37569434
Differentially Expressed Genes Regulating Glutathione Metabolism, Protein-Folding, and Unfolded Protein Response in Pancreatic β-Cells in Type 2 Diabetes Mellitus.
Elena Klyosova · Iuliia Azarova · Stepan Buikin · Alexey Polonikov
International journal of molecular sciences · 2023 doi:10.3390/ijms241512059
Paper
complete
Experiment
complete
Data
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Analysis
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Execution
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Complete file
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The present study was designed to identify differentially expressed genes (DEGs) encoding enzymes for glutathione metabolism and their impact on the expression levels of genes regulating protein folding and UPR in β-cells of T2D patients. The GEO transcriptome datasets of β-cells of diabetics and non-diabetics, GSE20966 and GSE81608, were analyzed for 142 genes of interest using limma and GREIN software, respectively. Diabetic β-cells showed dataset-specific patterns of DEGs (FDR ≤ 0.05) implicated in the regulation of glutathione metabolism (ANPEP, PGD, IDH2, and CTH), protein-folding (HSP90AB1, HSP90AA1, HSPA1B, HSPA8, BAG3, NDC1, NUP160, RLN1, and RPS19BP1), and unfolded protein response (CREB3L4, ERP27, and BID). The GCLC gene, encoding the catalytic subunit of glutamate-cysteine ligase, the first rate-limiting enzyme of glutathione biosynthesis, was moderately down-regulated in diabetic β-cells from both datasets (p ≤ 0.05). Regression analysis established that genes involved in the de novo synthesis of glutathione, GCLC, GCLM, and GSS affect the expression levels of genes encoding molecular chaperones and those involved in the UPR pathway. 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"GSM2158499", "GSM2158500", "GSM2158501", "GSM2158502", "GSM2158503", "GSM2158504", "GSM2158505", "GSM2158506", "GSM2158507", "GSM2158508", "GSM2158509", "GSM2158510", "GSM2158511", "GSM2158512", "GSM2158513", "GSM2158514", "GSM2158515", "GSM2158516", "GSM2158517", "GSM2158518", "GSM2158519", "GSM2158520", "GSM2158521", "GSM2158522", "GSM2158523", "GSM2158524", "GSM2158525", "GSM2158526", "GSM2158527", "GSM2158528", "GSM2158529", "GSM2158530", "GSM2158531", "GSM2158532", "GSM2158533", "GSM2158534", "GSM2158535", "GSM2158536", "GSM2158537", "GSM2158538", "GSM2158539", "GSM2158540", "GSM2158541", "GSM2158542", "GSM2158543", "GSM2158544", "GSM2158545", "GSM2158546", "GSM2158547", "GSM2158548", "GSM2158549", "GSM2158550", "GSM2158551", "GSM2158552", "GSM2158553", "GSM2158554", "GSM2158555", "GSM2158556", "GSM2158557", "GSM2158558", "GSM2158559", "GSM2158560", "GSM2158561", "GSM2158562", "GSM2158563", "GSM2158564", "GSM2158565", "GSM2158566", "GSM2158567", "GSM2158568", "GSM2158569", "GSM2158570", "GSM2158571", "GSM2158572", "GSM2158573", "GSM2158574", "GSM2158575", "GSM2158576", "GSM2158577", "GSM2158578", "GSM2158579", "GSM2158580", "GSM2158581", "GSM2158582", "GSM2158583", "GSM2158584", "GSM2158585", "GSM2158586", "GSM2158587", "GSM2158588", "GSM2158589", "GSM2158590", "GSM2158591", "GSM2158592", "GSM2158593", "GSM2158594", "GSM2158595", "GSM2158596", "GSM2158597", "GSM2158598", "GSM2158599", "GSM2158600", "GSM2158601", "GSM2158602", "GSM2158603", "GSM2158604", "GSM2158605", "GSM2158606", "GSM2158607", "GSM2158608", "GSM2158609", "GSM2158610", "GSM2158611", "GSM2158612", "GSM2158613", "GSM2158614", "GSM2158615", "GSM2158616", "GSM2158617", "GSM2158618", "GSM2158619", "GSM2158620", "GSM2158621", "GSM2158622", "GSM2158623", "GSM2158624", "GSM2158625", "GSM2158626", "GSM2158627", "GSM2158628", "GSM2158629", "GSM2158630", "GSM2158631", "GSM2158632", "GSM2158633", "GSM2158634", "GSM2158635", "GSM2158636", "GSM2158637", "GSM2158638", "GSM2158639", "GSM2158640", "GSM2158641", "GSM2158642", "GSM2158643", "GSM2158644", "GSM2158645", "GSM2158646", "GSM2158647", "GSM2158648", "GSM2158649", "GSM2158650", "GSM2158651", "GSM2158652", "GSM2158653", "GSM2158654", "GSM2158655", "GSM2158656", "GSM2158657", "GSM2158658", "GSM2158659", "GSM2158660", "GSM2158661", "GSM2158662", "GSM2158663", "GSM2158664", "GSM2158665", "GSM2158666", "GSM2158667", "GSM2158668", "GSM2158669", "GSM2158670", "GSM2158671", "GSM2158672", "GSM2158673", "GSM2158674", "GSM2158675", "GSM2158676", "GSM2158677", "GSM2158678", "GSM2158679", "GSM2158680", "GSM2158681", "GSM2158682", "GSM2158683", "GSM2158684", "GSM2158685", "GSM2158686", "GSM2158687", "GSM2158688", "GSM2158689", "GSM2158690", "GSM2158691", "GSM2158692", "GSM2158693", "GSM2158694", "GSM2158695", "GSM2158696", "GSM2158697", "GSM2158698", "GSM2158699", "GSM2158700", "GSM2158701", "GSM2158702", "GSM2158703", "GSM2158704", "GSM2158705", "GSM2158706", "GSM2158707", "GSM2158708", "GSM2158709", "GSM2158710", "GSM2158711", "GSM2158712", "GSM2158713", "GSM2158714", "GSM2158715", "GSM2158716", "GSM2158717", "GSM2158718", "GSM2158719", "GSM2158720", "GSM2158721", "GSM2158722", "GSM2158723", "GSM2158724", "GSM2158725", "GSM2158726", "GSM2158727", "GSM2158728", "GSM2158729", "GSM2158730", "GSM2158731", "GSM2158732", "GSM2158733", "GSM2158734", "GSM2158735", "GSM2158736", "GSM2158737", "GSM2158738", "GSM2158739", "GSM2158740", "GSM2158741", "GSM2158742", "GSM2158743", "GSM2158744", "GSM2158745", "GSM2158746", "GSM2158747", "GSM2158748", "GSM2158749", "GSM2158750", "GSM2158751", "GSM2158752", "GSM2158753", "GSM2158754", "GSM2158755", "GSM2158756", "GSM2158757", "GSM2158758", "GSM2158759", "GSM2158760", "GSM2158761", "GSM2158762", "GSM2158763", "GSM2158764", "GSM2158765", "GSM2158766", "GSM2158767", "GSM2158768", "GSM2158769", "GSM2158770", "GSM2158771", "GSM2158772", "GSM2158773", "GSM2158774", "GSM2158775", "GSM2158776", "GSM2158777", "GSM2158778", "GSM2158779", "GSM2158780", "GSM2158781", "GSM2158782", "GSM2158783", "GSM2158784", "GSM2158785", "GSM2158786", "GSM2158787", "GSM2158788", "GSM2158789", "GSM2158790", "GSM2158791", "GSM2158792", "GSM2158793", "GSM2158794", "GSM2158795", "GSM2158796", "GSM2158797", "GSM2158798", "GSM2158799", "GSM2158800", "GSM2158801", "GSM2158802", "GSM2158803", "GSM2158804", "GSM2158805", "GSM2158806", "GSM2158807", "GSM2158808", "GSM2158809", "GSM2158810", "GSM2158811", "GSM2158812", "GSM2158813", "GSM2158814", "GSM2158815", "GSM2158816", "GSM2158817", "GSM2158818", "GSM2158819", "GSM2158820", "GSM2158821", "GSM2158822", "GSM2158823", "GSM2158824", "GSM2158825", "GSM2158826", "GSM2158827", "GSM2158828", "GSM2158829", "GSM2158830", "GSM2158831", "GSM2158832", "GSM2158833", "GSM2158834", "GSM2158835", "GSM2158836", "GSM2158837", "GSM2158838", "GSM2158839", "GSM2158840", "GSM2158842", "GSM2158843", "GSM2158844", "GSM2158846", "GSM2158848", "GSM2158849", "GSM2158850", "GSM2158852", "GSM2158853", "GSM2158855", "GSM2158856", "GSM2158858", "GSM2158859", "GSM2158861", "GSM2158862", "GSM2158863", "GSM2158865", "GSM2158866", "GSM2158868", "GSM2158869", "GSM2158871", "GSM2158872", "GSM2158874", "GSM2158875", "GSM2158877", "GSM2158878", "GSM2158879", "GSM2158881", "GSM2158882", "GSM2158884", "GSM2158885", "GSM2158887", "GSM2158888", "GSM2158889", "GSM2158891", "GSM2158892", "GSM2158894", "GSM2158895", "GSM2158896", "GSM2158898", "GSM2158899", "GSM2158901", "GSM2158902", "GSM2158904", "GSM2158906", "GSM2158907", "GSM2158908", "GSM2158910", "GSM2158911", "GSM2158913", "GSM2158914", "GSM2158916", "GSM2158917", "GSM2158919", "GSM2158920", "GSM2158922", "GSM2158923", "GSM2158925", "GSM2158926", "GSM2158928", "GSM2158929", "GSM2158931", "GSM2158932", "GSM2158934", "GSM2158935", "GSM2158936", "GSM2158937", "GSM2158938", "GSM2158939", "GSM2158940", "GSM2158941", "GSM2158942", "GSM2158943", "GSM2158944", "GSM2158945", "GSM2158946", "GSM2158947", "GSM2158948", "GSM2158949", "GSM2158950", "GSM2158951", "GSM2158952", "GSM2158953", "GSM2158954", "GSM2158955", "GSM2158956", "GSM2158957", "GSM2158958", "GSM2158959", "GSM2158960", "GSM2158961", "GSM2158962", "GSM2158963", "GSM2158964", "GSM2158965", "GSM2158966", "GSM2158967", "GSM2158968", "GSM2158969", "GSM2158970", "GSM2158971", "GSM2158972", "GSM2158973", "GSM2158974", "GSM2158975", "GSM2158976", "GSM2158977", "GSM2158978", "GSM2158979", "GSM2158980", "GSM2158981", "GSM2158982", "GSM2158983", "GSM2158984", "GSM2158985", "GSM2158986", "GSM2158987", "GSM2158988", "GSM2158989", "GSM2158990", "GSM2158991", "GSM2158992", "GSM2158993", "GSM2158994", "GSM2158995", "GSM2158996", "GSM2158997", "GSM2158998", "GSM2158999", "GSM2159000", "GSM2159001", "GSM2159002", "GSM2159003", "GSM2159004", "GSM2159005", "GSM2159006", "GSM2159007", "GSM2159008", "GSM2159009", "GSM2159010", "GSM2159011", "GSM2159012", "GSM2159013", "GSM2159014", "GSM2159015", "GSM2159016", "GSM2159017", "GSM2159018", "GSM2159019", "GSM2159020", "GSM2159021", "GSM2159022", "GSM2159023", "GSM2159024", "GSM2159025", "GSM2159026", "GSM2159027", "GSM2159028", "GSM2159029", "GSM2159030", "GSM2159031", "GSM2159032", "GSM2159033", "GSM2159034", "GSM2159035", "GSM2159036", "GSM2159037", "GSM2159038", "GSM2159039", "GSM2159040", "GSM2159041", "GSM2159042", "GSM2159043", "GSM2159044", "GSM2159045", "GSM2159046", "GSM2159047", "GSM2159048", "GSM2159049", "GSM2159050", "GSM2159051", "GSM2159052", "GSM2159053", "GSM2159054", "GSM2159055", "GSM2159056", "GSM2159057", "GSM2159058", "GSM2159059", "GSM2159060", "GSM2159061", "GSM2159062", "GSM2159063", "GSM2159064", "GSM2159065", "GSM2159066", "GSM2159067", "GSM2159068", "GSM2159069", "GSM2159070", "GSM2159071", "GSM2159072", "GSM2159073", "GSM2159074", "GSM2159075", "GSM2159076", "GSM2159077", "GSM2159078", "GSM2159079", "GSM2159080", "GSM2159081", "GSM2159082", "GSM2159083", "GSM2159084", "GSM2159085", "GSM2159086", "GSM2159087", "GSM2159088", "GSM2159089", "GSM2159090", "GSM2159091", "GSM2159092", "GSM2159093", "GSM2159094", "GSM2159095", "GSM2159096", "GSM2159097", "GSM2159098", "GSM2159099", "GSM2159100", "GSM2159101", "GSM2159102", "GSM2159103", "GSM2159104", "GSM2159105", "GSM2159106", "GSM2159107", "GSM2159108", "GSM2159109", "GSM2159110", "GSM2159111", "GSM2159112", "GSM2159113", "GSM2159114", "GSM2159115", "GSM2159116", "GSM2159117", "GSM2159118", "GSM2159119", "GSM2159120", "GSM2159121", "GSM2159122", "GSM2159123", "GSM2159124", "GSM2159125", "GSM2159126", "GSM2159127", "GSM2159128", "GSM2159129", "GSM2159130", "GSM2159131", "GSM2159132", "GSM2159133", "GSM2159134", "GSM2159135", "GSM2159136", "GSM2159137", "GSM2159138", "GSM2159139", "GSM2159140", "GSM2159141", "GSM2159142", "GSM2159143", "GSM2159144", "GSM2159145", "GSM2159146", "GSM2159147", "GSM2159148", "GSM2159149", "GSM2159150", "GSM2159151", "GSM2159152", "GSM2159153", "GSM2159154", "GSM2159155", "GSM2159156", "GSM2159157", "GSM2159158", "GSM2159159", "GSM2159160", "GSM2159161", "GSM2159162", "GSM2159163", "GSM2159164", "GSM2159165", "GSM2159166", "GSM2159167", "GSM2159168", "GSM2159169", "GSM2159170", "GSM2159171", "GSM2159172", "GSM2159173", "GSM2159174", "GSM2159175", "GSM2159176", "GSM2159177", "GSM2159178", "GSM2159179", "GSM2159180", "GSM2159181", "GSM2159182", "GSM2159183", "GSM2159184", "GSM2159185", "GSM2159186", "GSM2159187", "GSM2159188", "GSM2159189", "GSM2159190", "GSM2159191", "GSM2159192", "GSM2159193", "GSM2159194", "GSM2159195", "GSM2159196", "GSM2159197", "GSM2159198", "GSM2159199", "GSM2159200", "GSM2159201", "GSM2159202", "GSM2159203", "GSM2159204", "GSM2159205", "GSM2159206", "GSM2159207", "GSM2159208", "GSM2159209", "GSM2159210", "GSM2159211", "GSM2159212", "GSM2159213", "GSM2159214", "GSM2159215", "GSM2159216", "GSM2159217", "GSM2159218", "GSM2159219", "GSM2159220", "GSM2159221", "GSM2159222", "GSM2159223", "GSM2159224", "GSM2159225", "GSM2159226", "GSM2159227", "GSM2159228", "GSM2159229", "GSM2159230", "GSM2159231", "GSM2159235", "GSM2159238", "GSM2159240", "GSM2159243", "GSM2159245", "GSM2159248", "GSM2159251", "GSM2159254", "GSM2159256", "GSM2159258", "GSM2159261", "GSM2159263", "GSM2159266", "GSM2159269", "GSM2159271", "GSM2159274", "GSM2159277", "GSM2159279", "GSM2159280", "GSM2159281", "GSM2159282", "GSM2159283", "GSM2159284", "GSM2159285", "GSM2159286", "GSM2159287", "GSM2159288", "GSM2159289", "GSM2159290", "GSM2159291", "GSM2159292", "GSM2159293", "GSM2159294", "GSM2159295", "GSM2159296", "GSM2159297", "GSM2159298", "GSM2159299", "GSM2159300", "GSM2159301", "GSM2159302", "GSM2159303", "GSM2159304", "GSM2159305", "GSM2159306", "GSM2159307", "GSM2159308", "GSM2159309", "GSM2159310", "GSM2159311", "GSM2159312", "GSM2159313", "GSM2159314", "GSM2159315", "GSM2159316", "GSM2159317", "GSM2159318", "GSM2159319", "GSM2159320", "GSM2159321", "GSM2159322", "GSM2159323", "GSM2159324", "GSM2159325", "GSM2159326", "GSM2159327", "GSM2159328", "GSM2159329", "GSM2159330", "GSM2159331", "GSM2159332", "GSM2159333", "GSM2159334", "GSM2159335", "GSM2159336", "GSM2159337", "GSM2159338", "GSM2159339", "GSM2159340", "GSM2159341", "GSM2159342", "GSM2159343", "GSM2159344", "GSM2159345", "GSM2159346", "GSM2159347", "GSM2159348", "GSM2159349", "GSM2159350", "GSM2159351", "GSM2159352", "GSM2159353", "GSM2159354", "GSM2159355", "GSM2159356", "GSM2159357", "GSM2159358", "GSM2159359", "GSM2159360", "GSM2159361", "GSM2159362", "GSM2159363", "GSM2159364", "GSM2159365", "GSM2159366", "GSM2159367", "GSM2159368", "GSM2159369", "GSM2159370", "GSM2159371", "GSM2159372", "GSM2159373", "GSM2159374", "GSM2159375", "GSM2159376", "GSM2159377", "GSM2159378", "GSM2159379", "GSM2159380", "GSM2159381", "GSM2159382", "GSM2159383", "GSM2159384", "GSM2159385", "GSM2159386", "GSM2159387", "GSM2159388", "GSM2159389", "GSM2159390", "GSM2159391", "GSM2159392", "GSM2159393", "GSM2159394", "GSM2159395", "GSM2159396", "GSM2159397", "GSM2159398", "GSM2159399", "GSM2159400", "GSM2159401", "GSM2159402", "GSM2159403", "GSM2159404", "GSM2159405", "GSM2159406", "GSM2159407", "GSM2159408", "GSM2159409", "GSM2159410", "GSM2159411", "GSM2159412", "GSM2159413", "GSM2159414", "GSM2159415", "GSM2159416", "GSM2159417", "GSM2159418", "GSM2159419", "GSM2159420", "GSM2159421", "GSM2159422", "GSM2159423", "GSM2159424", "GSM2159425", "GSM2159426", "GSM2159427", "GSM2159428", "GSM2159429", "GSM2159430", "GSM2159431", "GSM2159432", "GSM2159433", "GSM2159434", "GSM2159435", "GSM2159436", "GSM2159437", "GSM2159438", "GSM2159439", "GSM2159440", "GSM2159441", "GSM2159442", "GSM2159443", "GSM2159444", "GSM2159445", "GSM2159446", "GSM2159447", "GSM2159448", "GSM2159449", "GSM2159450", "GSM2159451", "GSM2159452", "GSM2159453", "GSM2159454", "GSM2159455", "GSM2159456", "GSM2159457", "GSM2159458", "GSM2159459", "GSM2159460", "GSM2159461", "GSM2159462", "GSM2159463", "GSM2159464", "GSM2159465", "GSM2159466", "GSM2159467", "GSM2159468", "GSM2159469", "GSM2159470", "GSM2159471", "GSM2159472", "GSM2159473", "GSM2159474", "GSM2159475", "GSM2159476", "GSM2159477", "GSM2159478", "GSM2159479", "GSM2159480", "GSM2159481", "GSM2159482", "GSM2159483", "GSM2159484", "GSM2159485", "GSM2159486", "GSM2159487", "GSM2159488", "GSM2159489", "GSM2159490", "GSM2159491", "GSM2159492", "GSM2159493", "GSM2159494", "GSM2159495", "GSM2159496", "GSM2159497", "GSM2159498", "GSM2159499", "GSM2159500", "GSM2159501", "GSM2159502", "GSM2159503", "GSM2159504", "GSM2159505", "GSM2159506", "GSM2159507", "GSM2159508", "GSM2159509", "GSM2159510", "GSM2159511", "GSM2159512", "GSM2159513", "GSM2159514", "GSM2159515", "GSM2159516", "GSM2159517", "GSM2159518", "GSM2159519", "GSM2159520", "GSM2159521", "GSM2159522", "GSM2159523", "GSM2159524", "GSM2159525", "GSM2159526", "GSM2159527", "GSM2159528", "GSM2159529", "GSM2159530", "GSM2159531", "GSM2159532", "GSM2159533", "GSM2159534", "GSM2159535", "GSM2159536", "GSM2159537", "GSM2159538", "GSM2159539", "GSM2159540", "GSM2159541", "GSM2159542", "GSM2159543", "GSM2159544", "GSM2159545", "GSM2159546", "GSM2159547", "GSM2159548", "GSM2159549", "GSM2159550", "GSM2159551", "GSM2159552", 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