Please use this identifier to cite or link to this item: http://hdl.handle.net/10553/35425
DC FieldValueLanguage
dc.contributor.authorTrinanes, J.en_US
dc.contributor.authorRodriguez-Rodriguez, A. E.en_US
dc.contributor.authorBrito Casillas, Yerayen_US
dc.contributor.authorWägner, Anaen_US
dc.contributor.authorDe Vries, A. P. J.en_US
dc.contributor.authorCuesto, G.en_US
dc.contributor.authorAcebes, A.en_US
dc.contributor.authorSalido Ruíz, Eduardoen_US
dc.contributor.authorTorres, A.en_US
dc.contributor.authorPorrini, E.en_US
dc.date.accessioned2018-04-17T12:07:16Z-
dc.date.available2018-04-17T12:07:16Z-
dc.date.issued2017en_US
dc.identifier.issn1600-6135en_US
dc.identifier.urihttp://hdl.handle.net/10553/35425-
dc.description.abstractβ Cell transcription factors such as forkhead box protein O1 (FoxO1), v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA), pancreatic and duodenal homeobox 1, and neuronal differentiation 1, are dysfunctional in type 2 diabetes mellitus (T2DM). Posttransplant diabetes mellitus resembles T2DM and reflects interaction between pretransplant insulin resistance and immunosuppressants, mainly calcineurin inhibitors (CNIs). We evaluated the effect of tacrolimus (TAC), cyclosporine A (CsA), and metabolic stressors (glucose plus palmitate) on insulinoma β cells in vitro and in pancreata of obese and lean Zucker rats. Cells were cultured for 5 days with 100 μM palmitate and 22 mM glucose; CsA (250 ng/mL) or TAC (15 ng/mL) were added in the last 48 h. Glucose plus palmitate increased nuclear FoxO1 and decreased nuclear MafA. TAC in addition to glucose plus palmitate magnified these changes in nuclear factors, whereas CsA did not. In addition to glucose plus palmitate, both drugs reduced insulin content, and TAC also affected insulin secretion. TAC withdrawal or conversion to CsA restored these changes. Similar results were observed in pancreata of obese animals on CNIs. TAC and CsA, in addition to glucose plus palmitate, induced comparable inhibition of calcineurin and nuclear factor of activated T cells (NFAT); therefore, TAC potentiates glucolipotoxicity in β cells, possibly by sharing common pathways of β cell dysfunction. TAC-induced β cell dysfunction is potentially reversible. Inhibition of the calcineurin–NFAT pathway may contribute to the diabetogenic effect of CNIs but does not explain the stronger effect of TAC compared with CsA.en_US
dc.languageengen_US
dc.relation.ispartofAmerican Journal of Transplantationen_US
dc.sourceAmerican Journal of Transplantation [ISSN 1600-6135], v. 17 (11), p. 2829-2840en_US
dc.subject32 Ciencias médicasen_US
dc.subject.otherComposite Tissue Allotransplantation
dc.subject.otherHand Transplantation
dc.subject.otherChilling Sensitivity
dc.subject.otherPhase-Transition
dc.subject.otherOvarian-Function
dc.subject.otherCryopreservation
dc.subject.otherImmunogenicity
dc.subject.otherOrgans
dc.subject.otherFace
dc.subject.otherAllografts
dc.titleDeciphering tacrolimus-induced toxicity in pancreatic β cellsen_US
dc.typeinfo:eu-repo/semantics/Articleen_US
dc.typeArticleen_US
dc.identifier.doi10.1111/ajt.14323
dc.identifier.scopus85020083575
dc.identifier.isi000413970100014-
dc.contributor.authorscopusid55151254000
dc.contributor.authorscopusid56770984900
dc.contributor.authorscopusid56236021400
dc.contributor.authorscopusid7401456520
dc.contributor.authorscopusid9037171800
dc.contributor.authorscopusid31168139200
dc.contributor.authorscopusid6603248438
dc.contributor.authorscopusid14023538500
dc.contributor.authorscopusid56712278500
dc.contributor.authorscopusid57202564967
dc.identifier.eissn1600-6143-
dc.description.lastpage2840-
dc.identifier.issue11-
dc.description.firstpage2829-
dc.relation.volume17-
dc.investigacionCiencias de la Saluden_US
dc.type2Artículoen_US
dc.identifier.wosWOS:000413970100014-
dc.contributor.daisngid4273649
dc.contributor.daisngid4769772
dc.contributor.daisngid3255019
dc.contributor.daisngid18980414
dc.contributor.daisngid595477
dc.contributor.daisngid5520880
dc.contributor.daisngid1237007
dc.contributor.daisngid61141
dc.contributor.daisngid571850
dc.contributor.daisngid664792
dc.contributor.wosstandardWOS:Trinanes, J
dc.contributor.wosstandardWOS:Rodriguez-Rodriguez, AE
dc.contributor.wosstandardWOS:Brito-Casillas, Y
dc.contributor.wosstandardWOS:Wagner, A
dc.contributor.wosstandardWOS:De Vries, APJ
dc.contributor.wosstandardWOS:Cuesto, G
dc.contributor.wosstandardWOS:Acebes, A
dc.contributor.wosstandardWOS:Salido, E
dc.contributor.wosstandardWOS:Torres, A
dc.contributor.wosstandardWOS:Porrini, E
dc.date.coverdateNoviembre 2017
dc.identifier.ulpgces
item.fulltextSin texto completo-
item.grantfulltextnone-
crisitem.author.deptDiabetes y endocrinología aplicada-
crisitem.author.deptIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.deptDepartamento de Ciencias Clínicas-
crisitem.author.deptDiabetes y endocrinología aplicada-
crisitem.author.deptIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.deptDepartamento de Ciencias Médicas y Quirúrgicas-
crisitem.author.orcid0000-0002-0707-7444-
crisitem.author.orcid0000-0002-7663-9308-
crisitem.author.parentorgIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.parentorgIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.fullNameBrito Casillas, Yeray-
crisitem.author.fullNameWägner, Anna Maria Claudia-
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