Metabolic regulation in progression to autoimmune diabetes.

Metabolic regulation in progression to autoimmune diabetes.

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...

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Autores principales: Marko Sysi-Aho, Andrey Ermolov, Peddinti V Gopalacharyulu, Abhishek Tripathi, Tuulikki Seppänen-Laakso, Johanna Maukonen, Ismo Mattila, Suvi T Ruohonen, Laura Vähätalo, Laxman Yetukuri, Taina Härkönen, Erno Lindfors, Janne Nikkilä, Jorma Ilonen, Olli Simell, Maria Saarela, Mikael Knip, Samuel Kaski, Eriika Savontaus, Matej Orešič
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2011
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Biology (General)
QH301-705.5
Acceso en línea:https://doaj.org/article/efa2394923bf45da8529c7eec04cc069
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spelling oai:doaj.org-article:efa2394923bf45da8529c7eec04cc0692021-11-18T05:51:49ZMetabolic regulation in progression to autoimmune diabetes.1553-734X1553-735810.1371/journal.pcbi.1002257https://doaj.org/article/efa2394923bf45da8529c7eec04cc0692011-10-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22046124/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Recent 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.Marko Sysi-AhoAndrey ErmolovPeddinti V GopalacharyuluAbhishek TripathiTuulikki Seppänen-LaaksoJohanna MaukonenIsmo MattilaSuvi T RuohonenLaura VähätaloLaxman YetukuriTaina HärkönenErno LindforsJanne NikkiläJorma IlonenOlli SimellMaria SaarelaMikael KnipSamuel KaskiEriika SavontausMatej OrešičPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 7, Iss 10, p e1002257 (2011)
institution DOAJ
collection DOAJ
language EN
topic Biology (General)
QH301-705.5
spellingShingle Biology (General)
QH301-705.5
Marko Sysi-Aho
Andrey Ermolov
Peddinti V Gopalacharyulu
Abhishek Tripathi
Tuulikki Seppänen-Laakso
Johanna Maukonen
Ismo Mattila
Suvi T Ruohonen
Laura Vähätalo
Laxman Yetukuri
Taina Härkönen
Erno Lindfors
Janne Nikkilä
Jorma Ilonen
Olli Simell
Maria Saarela
Mikael Knip
Samuel Kaski
Eriika Savontaus
Matej Orešič
Metabolic regulation in progression to autoimmune diabetes.
description 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.
format article
author Marko Sysi-Aho
Andrey Ermolov
Peddinti V Gopalacharyulu
Abhishek Tripathi
Tuulikki Seppänen-Laakso
Johanna Maukonen
Ismo Mattila
Suvi T Ruohonen
Laura Vähätalo
Laxman Yetukuri
Taina Härkönen
Erno Lindfors
Janne Nikkilä
Jorma Ilonen
Olli Simell
Maria Saarela
Mikael Knip
Samuel Kaski
Eriika Savontaus
Matej Orešič
author_facet Marko Sysi-Aho
Andrey Ermolov
Peddinti V Gopalacharyulu
Abhishek Tripathi
Tuulikki Seppänen-Laakso
Johanna Maukonen
Ismo Mattila
Suvi T Ruohonen
Laura Vähätalo
Laxman Yetukuri
Taina Härkönen
Erno Lindfors
Janne Nikkilä
Jorma Ilonen
Olli Simell
Maria Saarela
Mikael Knip
Samuel Kaski
Eriika Savontaus
Matej Orešič
author_sort Marko Sysi-Aho
title Metabolic regulation in progression to autoimmune diabetes.
title_short Metabolic regulation in progression to autoimmune diabetes.
title_full Metabolic regulation in progression to autoimmune diabetes.
title_fullStr Metabolic regulation in progression to autoimmune diabetes.
title_full_unstemmed Metabolic regulation in progression to autoimmune diabetes.
title_sort metabolic regulation in progression to autoimmune diabetes.
publisher Public Library of Science (PLoS)
publishDate 2011
url https://doaj.org/article/efa2394923bf45da8529c7eec04cc069
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