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  • Sen, ParthoTurku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland (author)

Metabolic alterations in immune cells associate with progression to type 1 diabetes

  • Article/chapterEnglish2020

Publisher, publication year, extent ...

  • 2020-02-11
  • Springer,2020
  • printrdacarrier

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  • LIBRIS-ID:oai:DiVA.org:oru-79927
  • https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-79927URI
  • https://doi.org/10.1007/s00125-020-05107-6DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:143059152URI

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  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Funding Agencies:Juvenile Diabetes Research Foundation 2-SRA-2014-159-Q-RAcademy of Finland 250114Academy of Finland (Personalised Health 2014 programme project)  292568FPU scholarship from the Spanish Ministry of Education, Culture and Sport  FPU15/02373
  • AIMS/HYPOTHESIS: Previous metabolomics studies suggest that type 1 diabetes is preceded by specific metabolic disturbances. The aim of this study was to investigate whether distinct metabolic patterns occur in peripheral blood mononuclear cells (PBMCs) of children who later develop pancreatic beta cell autoimmunity or overt type 1 diabetes.METHODS: In a longitudinal cohort setting, PBMC metabolomic analysis was applied in children who (1) progressed to type 1 diabetes (PT1D, n = 34), (2) seroconverted to ≥1 islet autoantibody without progressing to type 1 diabetes (P1Ab, n = 27) or (3) remained autoantibody negative during follow-up (CTRL, n = 10).RESULTS: During the first year of life, levels of most lipids and polar metabolites were lower in the PT1D and P1Ab groups compared with the CTRL group. Pathway over-representation analysis suggested alanine, aspartate, glutamate, glycerophospholipid and sphingolipid metabolism were over-represented in PT1D. Genome-scale metabolic models of PBMCs during type 1 diabetes progression were developed by using publicly available transcriptomics data and constrained with metabolomics data from our study. Metabolic modelling confirmed altered ceramide pathways, known to play an important role in immune regulation, as specifically associated with type 1 diabetes progression.CONCLUSIONS/INTERPRETATION: Our data suggest that systemic dysregulation of lipid metabolism, as observed in plasma, may impact the metabolism and function of immune cells during progression to overt type 1 diabetes.DATA AVAILABILITY: The GEMs for PBMCs have been submitted to BioModels (www.ebi.ac.uk/biomodels/), under accession number MODEL1905270001. The metabolomics datasets and the clinical metadata generated in this study were submitted to MetaboLights (https://www.ebi.ac.uk/metabolights/), under accession number MTBLS1015.

Subject headings and genre

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  • Dickens, Alex M.Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland (author)
  • López-Bascón, María AsunciónDepartment of Chemistry, Örebro University, Örebro, Sweden; Department of Analytical Chemistry, University of Córdoba, Córdoba, Spain; (author)
  • Lindeman, TuomasTurku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland (author)
  • Kemppainen, EskoTurku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland (author)
  • Lamichhane, SantoshTurku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland (author)
  • Rönkkö, TuukkaTurku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland (author)
  • Ilonen, JormaImmunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland; Clinical Microbiology, Turku University Hospital, Turku, Finland (author)
  • Toppari, JormaDepartment of Pediatrics and Adolescent Medicine, Turku University Hospital, Turku, Finland; Institute of Biomedicine, Centre for Integrative Physiology and Pharmacology, University of Turku, Turku, Finland. (author)
  • Veijola, RiittaDepartment of Pediatrics, PEDEGO Research Unit, Medical Research Centre, University of Oulu, Oulu, Finland; Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland; Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden (author)
  • Hyöty, HeikkiFaculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland; Fimlab Laboratories, Pirkanmaa Hospital District, Tampere, Finland (author)
  • Hyötyläinen, Tuulia,1971-Örebro universitet,Institutionen för naturvetenskap och teknik(Swepub:oru)tihn (author)
  • Knip, MikaelChildren's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Tampere Centre for Child Health Research, Tampere University Hospital, Tampere, Finland (author)
  • Oresic, Matej,1967-Örebro universitet,Institutionen för medicinska vetenskaper,Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland(Swepub:oru)moc (author)
  • Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, FinlandDepartment of Chemistry, Örebro University, Örebro, Sweden; Department of Analytical Chemistry, University of Córdoba, Córdoba, Spain; (creator_code:org_t)

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  • In:Diabetologia: Springer63:5, s. 1017-10310012-186X1432-0428

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