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Intra- and inter-individual metabolic profiling highlights carnitine and lysophosphatidylcholine pathways as key molecular defects in type 2 diabetes
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics. Uppsala University, Science for Life Laboratory, SciLifeLab.ORCID iD: 0000-0002-4922-8415
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.ORCID iD: 0000-0001-5498-3899
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2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 9653Article in journal (Refereed) Published
Abstract [en]

Type 2 diabetes (T2D) mellitus is a complex metabolic disease commonly caused by insulin resistance in several tissues. We performed a matched two-dimensional metabolic screening in tissue samples from 43 multi-organ donors. The intra-individual analysis was assessed across five key metabolic tissues (serum, visceral adipose tissue, liver, pancreatic islets and skeletal muscle), and the inter-individual across three different groups reflecting T2D progression. We identified 92 metabolites differing significantly between non-diabetes and T2D subjects. In diabetes cases, carnitines were significantly higher in liver, while lysophosphatidylcholines were significantly lower in muscle and serum. We tracked the primary tissue of origin for multiple metabolites whose alterations were reflected in serum. An investigation of three major stages spanning from controls, to pre-diabetes and to overt T2D indicated that a subset of lysophosphatidylcholines was significantly lower in the muscle of pre-diabetes subjects. Moreover, glycodeoxycholic acid was significantly higher in liver of pre-diabetes subjects while additional increase in T2D was insignificant. We confirmed many previously reported findings and substantially expanded on them with altered markers for early and overt T2D. Overall, the analysis of this unique dataset can increase the understanding of the metabolic interplay between organs in the development of T2D.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2019. Vol. 9, article id 9653
National Category
Endocrinology and Diabetes
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URN: urn:nbn:se:uu:diva-391017DOI: 10.1038/s41598-019-45906-5ISI: 000474222900010PubMedID: 31273253OAI: oai:DiVA.org:uu-391017DiVA, id: diva2:1344467
Funder
AstraZenecaSwedish Research Council FormaseSSENCE - An eScience CollaborationSwedish Diabetes AssociationErnfors FoundationAvailable from: 2019-08-21 Created: 2019-08-21 Last updated: 2019-08-21Bibliographically approved

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Diamanti, KlevCavalli, MarcoPan, GangPereira, Maria JGrabherr, ManfredRisérus, UlfEriksson, JanKomorowski, JanWadelius, Claes
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Computational Biology and BioinformaticsScience for Life Laboratory, SciLifeLabMedicinsk genetik och genomikClinical diabetology and metabolismDepartment of Medical Biochemistry and MicrobiologyClinical Nutrition and Metabolism
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