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Proteome- and Transcriptome-Driven Reconstruction of the Human Myocyte Metabolic Network and Its Use for Identification of Markers for Diabetes
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2015 (Engelska)Ingår i: Cell reports, ISSN 2211-1247, E-ISSN 2211-1247, Vol. 11, nr 6, s. 921-933Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Skeletal myocytes are metabolically active and susceptible to insulin resistance and are thus implicated in type 2 diabetes (T2D). This complex disease involves systemic metabolic changes, and their elucidation at the systems level requires genome-wide data and biological networks. Genome-scale metabolic models (GEMs) provide a network context for the integration of high-throughput data. We generated myocyte-specific RNA-sequencing data and investigated their correlation with proteome data. These data were then used to reconstruct a comprehensive myocyte GEM. Next, we performed a meta-analysis of six studies comparing muscle transcription in T2D versus healthy subjects. Transcriptional changes were mapped on the myocyte GEM, revealing extensive transcriptional regulation in T2D, particularly around pyruvate oxidation, branched-chain amino acid catabolism, and tetrahydrofolate metabolism, connected through the downregulated dihydrolipoamide dehydrogenase. Strikingly, the gene signature underlying this metabolic regulation successfully classifies the disease state of individual samples, suggesting that regulation of these pathways is a ubiquitous feature of myocytes in response to T2D.

Ort, förlag, år, upplaga, sidor
2015. Vol. 11, nr 6, s. 921-933
Nyckelord [en]
Gene-Set Analysis, Insulin-Resistance, Skeletal-Muscle, Expression Data, Oxidative-Phosphorylation, Amino-Acids, Integration, Obesity, Quantification, Hyperglycemia
Nationell ämneskategori
Cellbiologi
Identifikatorer
URN: urn:nbn:se:kth:diva-169267DOI: 10.1016/j.celrep.2015.04.010ISI: 000354406900009PubMedID: 25937284Scopus ID: 2-s2.0-84929276343OAI: oai:DiVA.org:kth-169267DiVA, id: diva2:821457
Forskningsfinansiär
Science for Life Laboratory - a national resource center for high-throughput molecular bioscienceKnut och Alice Wallenbergs StiftelseNovo Nordisk
Anmärkning

QC 20150615

Tillgänglig från: 2015-06-15 Skapad: 2015-06-12 Senast uppdaterad: 2020-03-10Bibliografiskt granskad

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Uhlén, Mathias

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Uhlén, MathiasNielsen, Jens
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Proteomik och nanobioteknologiScience for Life Laboratory, SciLifeLabGenteknologi
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Cell reports
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