Dataset Information

Intra- and inter-individual metabolic profiling highlights carnitine and lysophosphatidylcholine pathways as key molecular defects in type-2 diabetes

ABSTRACT: In this study we explored a unique cohort of 43 samples to build a map of metabolites varying in T2D across five different tissues (subcutaneous adipose tissue, liver, pancreatic islets, skeletal muscle and blood serum). The samples originate from the Excellence in Diabetes biobank (EXODIAB) in Sweden. To our knowledge, this is the first attempt to create a map of metabolites across various metabolic-relevant tissues for the same cohort of individuals. In total we identified 286 unique metabolites, 32% of which were significantly altered between non-diabetes and T2D. We found evidence that amino acids (AAs) and bile acids are elevated for specific tissues in T2D and significantly associated to the percentage of glycosylated hemoglobin A1c (HbA1c). We showed that carnitines and lysophosphatidylcholines (LPCs) are the most significantly altered metabolites in muscle, liver and serum in T2D. Finally, we attempted to explore the progression to overt T2D and suggest potential biomarkers in the early development of T2D, i.e. from non-diabetes to pre-diabetes to T2D.

INSTRUMENT(S): Agilent 6550 iFunnel Accurate-Mass UHPLC-QTOFMSMS (negative mode), LECO Pegasus III, GCTOFMS, Agilent 6550 iFunnel Accurate-Mass UHPLC-QTOFMSMS (positive mode)

SUBMITTER: Klev Diamanti

PROVIDER: MTBLS690 | MetaboLights | 2018-10-08

REPOSITORIES: MetaboLights

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Intra- and inter-individual metabolic profiling highlights carnitine and lysophosphatidylcholine pathways as key molecular defects in type 2 diabetes.

Diamanti Klev K Cavalli Marco M Pan Gang G Pereira Maria J MJ Kumar Chanchal C Skrtic Stanko S Grabherr Manfred M Risérus Ulf U Eriksson Jan W JW Komorowski Jan J Wadelius Claes C

Scientific reports 20190704 1

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 differ ...[more]

PMID: 31273253

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Project description:Dysregulation in expression of microRNAs (miRNAs) in various tissues has been linked to a wide spectrum of diseases, including Type 2 Diabetes mellitus (T2D). In this study, we compared the expression profiles of miRNAs in blood samples from Impaired Fasting Glucose (IFG) and T2D male patients with tissues from T2D rat models. Healthy adult males with no past history of T2D (n=158) and with desirable cholesterol and blood pressure profiles were enrolled in this study. They were then classified according to fasting glucose levels to have T2D, IFG or as healthy controls (CTL), for comparison of miRNA expression profiles. Employing miRNA microarray, we identified ‘signature miRNAs’ in peripheral blood samples that distinguished IFG and T2D. Eight selected miRNAs were further validated using stem-loop real-time RT-PCR. miR-144 expression was found to be dysregulated in Type 2 Diabetes, wherein its expression was significantly higher than in healthy controls. Insulin receptor substrate 1 (IRS1) has been predicted to be a potential target of miR-144. Consistent with this observation, IRS1 mRNA and protein levels, verified by quantitative real-time PCR and western blotting respectively, were found to be down-regulated. Using luciferase assay, we further demonstrated that miR-144 directly targets IRS1 and showed its effects on protein expression via immunocytochemistry. From this cross-sectional study in humans, we have identified signature miRNAs which could explain the pathogenesis of T2D. Whether miRNAs like miR-144 could be potential therapeutic targets for management of T2D will need to be explored by further mechanistic and functional studies. miRNA profiling of tissues from T2D rat models. Total RNA (plus miRNAs) was isolated using a modification of the RiboPure™-Blood kit from Ambion (Austin,TX) according to the manufacturer’s protocol. The concentration of total RNA and integrity were determined by using Nano-Drop ND-1000 Spectrophotometry (NanoDrop Tech, Rockland, Del) and gel electrophoresis respectively.

Dataset Information

Intra- and inter-individual metabolic profiling highlights carnitine and lysophosphatidylcholine pathways as key molecular defects in type-2 diabetes

Publications

Intra- and inter-individual metabolic profiling highlights carnitine and lysophosphatidylcholine pathways as key molecular defects in type 2 diabetes.

Similar Datasets

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