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Metabolic regulation in progression to autoimmune diabetes

Sysi-Aho, Marko (author)
VTT Technical Research Centre of Finland, Espoo, Finland
Ermolov, Andrey (author)
Aalto University School of Science, Department of Information and Computer Science, Helsinki Institute for Information Technology HIIT, Espoo, Finland
Gopalacharyulu, Peddinti V. (author)
VTT Technical Research Centre of Finland, Espoo, Finland
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Tripathi, Abhishek (author)
Helsinki Institute for Information Technology HIIT, Department of Computer Science, University of Helsinki, Finland
Seppänen-Laakso, Tuulikki (author)
VTT Technical Research Centre of Finland, Espoo, Finland
Maukonen, Johanna (author)
VTT Technical Research Centre of Finland, Espoo, Finland
Mattila, Ismo (author)
VTT Technical Research Centre of Finland, Espoo, Finland
Ruohonen, Suvi T. (author)
Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland
Vähätalo, Laura (author)
Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland
Yetukuri, Laxman (author)
VTT Technical Research Centre of Finland, Espoo, Finland
Härkönen, Taina (author)
Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland
Lindfors, Erno (author)
VTT Technical Research Centre of Finland, Espoo, Finland
Nikkilä, Janne (author)
Finnish Red Cross Blood Service, Helsinki, Finland
Ilonen, Jorma (author)
epartment of Clinical Microbiology, University of Eastern Finland, Kuopio, Finland; Immunogenetics Laboratory, University of Turku, Turku, Finland
Simell, Olli (author)
Department of Pediatrics, University of Turku, Turku, Finland
Saarela, Maria (author)
VTT Technical Research Centre of Finland, Espoo, Finland
Knip, Mikael (author)
ospital for Children and Adolescents, University of Helsinki, Helsinki, Finland, Department of Pediatrics, Tampere University Hospital, Tampere, Finland; Folkhälsan Research Center, Helsinki, Finland
Kaski, Samuel (author)
Aalto University School of Science, Department of Information and Computer Science, Helsinki Institute for Information Technology HIIT, Espoo, Finland; Helsinki Institute for Information Technology HIIT, Department of Computer Science, University of Helsinki, Finland
Savontaus, Eriika (author)
Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland; Unit of Clinical Pharmacology, Turku University Hospital, Turku, Finland
Oresic, Matej, 1967- (author)
VTT Technical Research Centre of Finland, Espoo, Finland; Institute of Molecular Medicine Finland FIMM, Helsinki, Finland
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 (creator_code:org_t)
2011-10-27
2011
English.
In: PloS Computational Biology. - : Public Library of Science (PLoS). - 1553-734X .- 1553-7358. ; 7:10
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https://doi.org/10.1...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Recent 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

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