Please use this identifier to cite or link to this item:
Full metadata record
DC FieldValueLanguage
dc.contributor.authorunicampVieira, Pedro Manoel Mendes de Moraes-
dc.titlePAHSAs attenuate immune responses and promote beta cell survival in autoimmune diabetic micept_BR
dc.contributor.authorSyed, Ismail-
dc.contributor.authorCelis, Maria F. Rubin de-
dc.contributor.authorMohan, James F.-
dc.contributor.authorMoraes-Vieira, Pedro M.-
dc.contributor.authorVijayakumar, Archana-
dc.contributor.authorNelson, Andrew T.-
dc.contributor.authorSiegel, Dionicio-
dc.contributor.authorSaghatelian, Alan-
dc.contributor.authorMathis, Diane-
dc.contributor.authorKahn, Barbara B.-
dc.subjectCélulas secretoras de insulinapt_BR
dc.subject.otherlanguageInsulin-secreting cellspt_BR
dc.description.abstractPalmitic acid esters of hydroxy stearic acids (PAHSAs) are endogenous antidiabetic and antiinflammatory lipids. Here, we show that PAHSAs protect against type 1 diabetes (T1D) and promote beta cell survival and function. Daily oral PAHSA administration to nonobese diabetic (NOD) mice delayed the onset of T1D and markedly reduced the incidence of T1D, whether PAHSAs were started before or after insulitis was established. PAHSAs reduced T and B cell infiltration and CD4(+) and CD8(+) T cell activation, while increasing Treg activation in pancreata of NOD mice. PAHSAs promoted beta cell proliferation in both NOD mice and MINE cells and increased the number of beta cells in NOD mice. PAHSAs attenuated cytokine-induced apoptotic and necrotic beta cell death and increased beta cell viability. The mechanism appears to involve a reduction of ER stress and MAPK signaling, since PAHSAs lowered ER stress in NOD mice, suppressed thapsigargin-induced PARP cleavage in human islets. and attenuated ERK1/2 and JNK1/2 activation in MINE cells. This appeared to be mediated in part by glucagon-like peptide 1 receptor (GLP-1R) and not the G protein-coupled receptor GPR40. PAHSAs also prevented impairment of glucose-stimulated insulin secretion and improved glucose tolerance in NOD mice. Thus, PAHSAs delayed the onset of T1D and reduced its incidence by attenuating immune responses and exerting direct protective effects on beta cell survival and functionpt_BR
dc.relation.ispartofJournal of clinical investigationpt_BR
dc.relation.ispartofabbreviationJ clin investpt_BR
dc.publisher.cityAnn Arbor, MIpt_BR
dc.publisher.countryEstados Unidospt_BR
dc.publisherAmerican Society for Clinical Investigationpt_BR
dc.description.provenanceSubmitted by Thais de Brito Barroso ( on 2020-05-06T21:22:28Z No. of bitstreams: 0. Added 1 bitstream(s) on 2020-08-27T19:16:58Z : No. of bitstreams: 1 000484368600028.pdf: 5924097 bytes, checksum: 4679ecfa0e92f6b6b899d6e8f8747afd (MD5)en
dc.description.provenanceMade available in DSpace on 2020-05-06T21:22:28Z (GMT). No. of bitstreams: 0 Previous issue date: 2019en
dc.contributor.departmentDepartamento de Genética e Evoluçãopt_BR
dc.contributor.unidadeInstituto de Biologiapt_BR
dc.type.formArtigo de pesquisapt_BR
Appears in Collections:IB - Artigos e Outros Documentos

Files in This Item:
File Description SizeFormat 
000484368600028.pdf5.79 MBAdobe PDFView/Open

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.