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Intra- and inter-in...
Intra- and inter-individual metabolic profiling highlights carnitine and lysophosphatidylcholine pathways as key molecular defects in type 2 diabetes
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- Diamanti, Klev (författare)
- Uppsala universitet,Beräkningsbiologi och bioinformatik,Science for Life Laboratory, SciLifeLab
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- Cavalli, Marco (författare)
- Uppsala universitet,Medicinsk genetik och genomik,Science for Life Laboratory, SciLifeLab
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- Pan, Gang (författare)
- Uppsala universitet,Medicinsk genetik och genomik,Science for Life Laboratory, SciLifeLab
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- Pereira, Maria J, 1981- (författare)
- Uppsala universitet,Klinisk diabetologi och metabolism
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- Kumar, C (författare)
- AstraZeneca, R&D BioPharmaceut, Translat Sci & Expt Med, Early Cardiovasc Renal & Metab, Gothenburg, Sweden;Karolinska Inst, AstraZeneca Integrated CardioMetab Ctr KI AZ ICMC, Dept Med, Huddinge, Sweden
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- Skrtic, S (författare)
- AstraZeneca AB, Pharmaceut Technol & Dev, Gothenburg, Sweden;Sahlgrens Univ Hosp, Dept Med, Gothenburg, Sweden
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- Grabherr, Manfred (författare)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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- Risérus, Ulf, 1967- (författare)
- Uppsala universitet,Klinisk nutrition och metabolism
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- Eriksson, Jan (författare)
- Uppsala universitet,Klinisk diabetologi och metabolism
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- Komorowski, Jan (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Beräkningsbiologi och bioinformatik,Polish Acad Sci, Inst Comp Sci, Warsaw, Poland
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- Wadelius, Claes, 1955- (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Medicinsk genetik och genomik
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(creator_code:org_t)
- 2019-07-04
- 2019
- Engelska.
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 9653-
- Relaterad länk:
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https://www.nature.c...
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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http://kipublication...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
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- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
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Diamanti, Klev
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Cavalli, Marco
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Pan, Gang
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Pereira, Maria J ...
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Kumar, C
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Skrtic, S
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visa fler...
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Grabherr, Manfre ...
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Risérus, Ulf, 19 ...
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Eriksson, Jan
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Komorowski, Jan
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Wadelius, Claes, ...
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- MEDICIN OCH HÄLSOVETENSKAP
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Karolinska Institutet
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Uppsala universitet