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  • Nowak, ChristophKarolinska Institutet,Uppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab,Karolinska Inst, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden,Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden; Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden (author)

Glucose challenge metabolomics implicates medium-chain acylcarnitines in insulin resistance

  • Article/chapterEnglish2018

Publisher, publication year, extent ...

  • 2018-06-06
  • Springer Science and Business Media LLC,2018
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-357687
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-357687URI
  • https://doi.org/10.1038/s41598-018-26701-0DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-74362URI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:du-27782URI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:138471704URI

Supplementary language notes

  • Language:English
  • Summary in:English

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

Notes

  • Tove Fall and Erik Ingelsson contributed equally to this work.
  • Insulin resistance (IR) predisposes to type 2 diabetes and cardiovascular disease but its causes are incompletely understood. Metabolic challenges like the oral glucose tolerance test (OGTT) can reveal pathogenic mechanisms. We aimed to discover associations of IR with metabolite trajectories during OGTT. In 470 non-diabetic men (age 70.6 +/- 0.6 years), plasma samples obtained at 0, 30 and 120 minutes during an OGTT were analyzed by untargeted liquid chromatography-mass spectrometry metabolomics. IR was assessed with the hyperinsulinemic-euglycemic clamp method. We applied age-adjusted linear regression to identify metabolites whose concentration change was related to IR. Nine trajectories, including monounsaturated fatty acids, lysophosphatidylethanolamines and a bile acid, were significantly associated with IR, with the strongest associations observed for medium-chain acylcarnitines C10 and C12, and no associations with L-carnitine or C2-, C8-, C14- or C16-carnitine. Concentrations of C10-and C12-carnitine decreased during OGTT with a blunted decline in participants with worse insulin resistance. Associations persisted after adjustment for obesity, fasting insulin and fasting glucose. In mouse 3T3-L1 adipocytes exposed to different acylcarnitines, we observed blunted insulin-stimulated glucose uptake after treatment with C10-or C12-carnitine. In conclusion, our results identify medium-chain acylcarnitines as possible contributors to IR.

Subject headings and genre

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  • Hetty, SusanneUppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab,Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden(Swepub:uu)sustr921 (author)
  • Salihovic, SamiraUppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab,Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden(Swepub:oru)sasc (author)
  • Castillejo-Lopez, CasimiroUppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab,Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden(Swepub:uu)cacas173 (author)
  • Ganna, AndreaMassachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA;Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA;Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA;Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden,Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (author)
  • Cook, Naomi L.Uppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab,Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden,Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden,Kardiovaskulär epidemiologi(Swepub:uu)larslind (author)
  • Broeckling, Corey D.Colorado State Univ, Prote & Metabol Facil, Ft Collins, CO 80523 USA,Proteomics and Metabolomics Facility, Colorado State University, Fort Collins, CO, USA (author)
  • Prenni, Jessica E.Colorado State Univ, Prote & Metabol Facil, Ft Collins, CO 80523 USA,Proteomics and Metabolomics Facility, Colorado State University, Fort Collins, CO, USA (author)
  • Shen, XiaKarolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden;Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland,Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK (author)
  • Giedraitis, VilmantasUppsala universitet,Geriatrik,Department of Public Health and Caring Sciences, Geriatrics, Uppsala University, Uppsala, Sweden(Swepub:uu)vigie517 (author)
  • Ärnlöv, Johan,1970-Karolinska Institutet,Högskolan Dalarna,Medicinsk vetenskap,Karolinska institutet,Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden;Karolinska Inst, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden(Swepub:du)jan (author)
  • Lind, LarsUppsala universitet,Kardiovaskulär epidemiologi(Swepub:uu)larslind (author)
  • Berne, ChristianUppsala universitet,Klinisk diabetologi och metabolism,Department of Medical Sciences, Clinical Diabetology and Metabolism, Uppsala University, Uppsala, Sweden(Swepub:uu)chber255 (author)
  • Sundström, JohanUppsala universitet,Kardiovaskulär epidemiologi,Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden(Swepub:uu)johasund (author)
  • Fall, Tove,1979-Uppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylär epidemiologi,Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden(Swepub:uu)tovfa878 (author)
  • Ingelsson, Erik,1975-Uppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylär epidemiologi,Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA,Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden; Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA; Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA(Swepub:uu)ering425 (author)
  • Uppsala universitetMolekylär epidemiologi (creator_code:org_t)

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