Intra- and inter-individual metabolic profiling highlights carnitine and lysophosphatidylcholine pathways as key molecular defects in type 2 diabetes
PBN-AR
Instytucja
Instytut Podstaw Informatyki Polskiej Akademii Nauk
Informacje podstawowe
Główny język publikacji
angielski
Czasopismo
Scientific Reports
ISSN
2045-2322
EISSN
Wydawca
DOI
URL
Rok publikacji
2019
Numer zeszytu
Strony od-do
9653:1-13
Numer tomu
9
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Open access
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Creative Commons — Uznanie autorstwa
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Data udostępnienia w sposób otwarty
Streszczenia
Język
en
Treść
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.
Inne
System-identifier
IPIPAN-A-5701
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