Metabolic regulation in progression to autoimmune diabetes

dc.contributorAalto Universityen
dc.contributor.authorSysi-Aho, Markoen_US
dc.contributor.authorErmolov, Andreyen_US
dc.contributor.authorGopalacharyulu, Peddinti V.en_US
dc.contributor.authorTripathi, Abhisheken_US
dc.contributor.authorSeppänen-Laakso, Tuulikkien_US
dc.contributor.authorMaukonen, Johannaen_US
dc.contributor.authorMattila, Ismoen_US
dc.contributor.authorRuohonen, Suvi T.en_US
dc.contributor.authorVähätalo, Lauraen_US
dc.contributor.authorYetukuri, Laxmanen_US
dc.contributor.authorHärkönen, Tainaen_US
dc.contributor.authorLindfors, Ernoen_US
dc.contributor.authorNikkilä, Janneen_US
dc.contributor.authorIlonen, Jormaen_US
dc.contributor.authorSimell, Ollien_US
dc.contributor.authorSaarela, Mariaen_US
dc.contributor.authorKnip, Mikaelen_US
dc.contributor.authorKaski, Samuelen_US
dc.contributor.authorSavontaus, Eriikaen_US
dc.contributor.authorOresic, Matejen_US
dc.contributor.departmentHelsinki Insititute for Information Technology HIITen
dc.contributor.departmentTietojenkäsittelytieteen laitoen
dc.descriptionVK: airc hiit
dc.description.abstractRecent evidence from serum metabolomics indicates that specific metabolic disturbances precede β-cell autoimmunity in humans and can be used to identify those children who subsequently progress to type 1 diabetes. The mechanisms behind these disturbances are unknown. Here we show the specificity of the pre-autoimmune metabolic changes, as indicated by their conservation in a murine model of type 1 diabetes. We performed a study in non-obese prediabetic (NOD) mice which recapitulated the design of the human study and derived the metabolic states from longitudinal lipidomics data. We show that female NOD mice who later progress to autoimmune diabetes exhibit the same lipidomic pattern as prediabetic children. These metabolic changes are accompanied by enhanced glucose-stimulated insulin secretion, normoglycemia, upregulation of insulinotropic amino acids in islets, elevated plasma leptin and adiponectin, and diminished gut microbial diversity of the Clostridium leptum group. Together, the findings indicate that autoimmune diabetes is preceded by a state of increased metabolic demands on the islets resulting in elevated insulin secretion and suggest alternative metabolic related pathways as therapeutic targets to prevent diabetes.en
dc.description.versionPeer revieweden
dc.identifier.citationSysi-Aho, M, Ermolov, A, Gopalacharyulu, P V, Tripathi, A, Seppänen-Laakso, T, Maukonen, J, Mattila, I, Ruohonen, S T, Vähätalo, L, Yetukuri, L, Härkönen, T, Lindfors, E, Nikkilä, J, Ilonen, J, Simell, O, Saarela, M, Knip, M, Kaski, S, Savontaus, E & Oresic, M 2011, ' Metabolic regulation in progression to autoimmune diabetes ', PLoS computational biology, vol. 7, no. 10, e1002257, pp. 1-16 .
dc.identifier.otherPURE UUID: a00dab3c-4ce5-4a02-ba18-c54e36146e5den_US
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dc.relation.ispartofseriesPLOS COMPUTATIONAL BIOLOGYen
dc.relation.ispartofseriesVolume 7, issue 10en
dc.titleMetabolic regulation in progression to autoimmune diabetesen
dc.typeA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessäfi