Skeletal muscle proteomes reveal downregulation of mitochondrial proteins in transition from prediabetes into type 2 diabetes
Summary: Skeletal muscle insulin resistance is a central defect in the pathogenesis of type 2 diabetes (T2D). Here, we analyzed skeletal muscle proteome in 148 vastus lateralis muscle biopsies obtained from men covering all glucose tolerance phenotypes: normal, impaired fasting glucose (IFG), impair...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-07-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004221006805 |
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| author | Tiina Öhman Jaakko Teppo Neeta Datta Selina Mäkinen Markku Varjosalo Heikki A. Koistinen |
| author_facet | Tiina Öhman Jaakko Teppo Neeta Datta Selina Mäkinen Markku Varjosalo Heikki A. Koistinen |
| author_sort | Tiina Öhman |
| collection | DOAJ |
| description | Summary: Skeletal muscle insulin resistance is a central defect in the pathogenesis of type 2 diabetes (T2D). Here, we analyzed skeletal muscle proteome in 148 vastus lateralis muscle biopsies obtained from men covering all glucose tolerance phenotypes: normal, impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and T2D. Skeletal muscle proteome was analyzed by a sequential window acquisition of all theoretical mass spectra (SWATH-MS) proteomics technique. Our data indicate a downregulation in several proteins involved in mitochondrial electron transport or respiratory chain complex assembly already in IFG and IGT muscles, with most profound decreases observed in T2D. Additional phosphoproteomic analysis reveals altered phosphorylation in several signaling pathways in IFG, IGT, and T2D muscles, including those regulating glucose metabolic processes, and the structure of muscle cells. These data reveal several alterations present in skeletal muscle already in prediabetes and highlight impaired mitochondrial energy metabolism in the trajectory from prediabetes into T2D. |
| first_indexed | 2024-12-21T20:28:34Z |
| format | Article |
| id | doaj.art-897bb0a30668417b8984615273780213 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-21T20:28:34Z |
| publishDate | 2021-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-897bb0a30668417b89846152737802132022-12-21T18:51:18ZengElsevieriScience2589-00422021-07-01247102712Skeletal muscle proteomes reveal downregulation of mitochondrial proteins in transition from prediabetes into type 2 diabetesTiina Öhman0Jaakko Teppo1Neeta Datta2Selina Mäkinen3Markku Varjosalo4Heikki A. Koistinen5University of Helsinki, Molecular Systems Biology Research Group and Proteomics Unit, Institute of Biotechnology, 00014 Helsinki, FinlandUniversity of Helsinki, Molecular Systems Biology Research Group and Proteomics Unit, Institute of Biotechnology, 00014 Helsinki, Finland; University of Helsinki, Drug Research Program, Faculty of Pharmacy, 00014 Helsinki, FinlandUniversity of Helsinki, Department of Medicine, Helsinki University Hospital, Haartmaninkatu 4, PO BOX 340, 00029 HUS, Helsinki, Finland; Minerva Foundation Institute for Medical Research, Tukholmankatu 8, 00290 Helsinki, FinlandUniversity of Helsinki, Department of Medicine, Helsinki University Hospital, Haartmaninkatu 4, PO BOX 340, 00029 HUS, Helsinki, Finland; Minerva Foundation Institute for Medical Research, Tukholmankatu 8, 00290 Helsinki, FinlandUniversity of Helsinki, Molecular Systems Biology Research Group and Proteomics Unit, Institute of Biotechnology, 00014 Helsinki, FinlandUniversity of Helsinki, Department of Medicine, Helsinki University Hospital, Haartmaninkatu 4, PO BOX 340, 00029 HUS, Helsinki, Finland; Minerva Foundation Institute for Medical Research, Tukholmankatu 8, 00290 Helsinki, Finland; Corresponding authorSummary: Skeletal muscle insulin resistance is a central defect in the pathogenesis of type 2 diabetes (T2D). Here, we analyzed skeletal muscle proteome in 148 vastus lateralis muscle biopsies obtained from men covering all glucose tolerance phenotypes: normal, impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and T2D. Skeletal muscle proteome was analyzed by a sequential window acquisition of all theoretical mass spectra (SWATH-MS) proteomics technique. Our data indicate a downregulation in several proteins involved in mitochondrial electron transport or respiratory chain complex assembly already in IFG and IGT muscles, with most profound decreases observed in T2D. Additional phosphoproteomic analysis reveals altered phosphorylation in several signaling pathways in IFG, IGT, and T2D muscles, including those regulating glucose metabolic processes, and the structure of muscle cells. These data reveal several alterations present in skeletal muscle already in prediabetes and highlight impaired mitochondrial energy metabolism in the trajectory from prediabetes into T2D.http://www.sciencedirect.com/science/article/pii/S2589004221006805Molecular biologyDiabetologyProteomics |
| spellingShingle | Tiina Öhman Jaakko Teppo Neeta Datta Selina Mäkinen Markku Varjosalo Heikki A. Koistinen Skeletal muscle proteomes reveal downregulation of mitochondrial proteins in transition from prediabetes into type 2 diabetes iScience Molecular biology Diabetology Proteomics |
| title | Skeletal muscle proteomes reveal downregulation of mitochondrial proteins in transition from prediabetes into type 2 diabetes |
| title_full | Skeletal muscle proteomes reveal downregulation of mitochondrial proteins in transition from prediabetes into type 2 diabetes |
| title_fullStr | Skeletal muscle proteomes reveal downregulation of mitochondrial proteins in transition from prediabetes into type 2 diabetes |
| title_full_unstemmed | Skeletal muscle proteomes reveal downregulation of mitochondrial proteins in transition from prediabetes into type 2 diabetes |
| title_short | Skeletal muscle proteomes reveal downregulation of mitochondrial proteins in transition from prediabetes into type 2 diabetes |
| title_sort | skeletal muscle proteomes reveal downregulation of mitochondrial proteins in transition from prediabetes into type 2 diabetes |
| topic | Molecular biology Diabetology Proteomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004221006805 |
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