Dysregulated skeletal muscle myosin super-relaxation and energetics in male participants with type 2 diabetes mellitus.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40295335", "kind": "science-record", "revision": 3, "content_hash": "sha256:650e58a1356ef50d3727f08d1df9e5b6a2b76ed7a514260e92d38252feb9729c", "created_at": "2026-11-01T20:30:27Z", "updated_at": "2026-11-01T22:13:58Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Dysregulated skeletal muscle myosin super-relaxation and energetics in male participants with type 2 diabetes mellitus.", "doi": "10.1007/s00125-025-06436-0", "pmid": "40295335", "authors": ["Christopher T A Lewis", "Roger Moreno-Justicia", "Lola Savoure", "Enrique Calvo", "Agata Bak", "Jenni Laitila", "Robert A E Seaborne", "Steen Larsen", "Hiroyuki Iwamoto", "Marina Cefis", "Jose A Morais", "Gilles Gouspillou", "Jorge Alegre-Cebollada", "Thomas J Hawke", "Jesús Vazquez", "Miquel Adrover", "Vincent Marcangeli", "Rami Hammad", "Jordan Granet", "Pierrette Gaudreau", "Mylène Aubertin-Leheudre", "Marc Bélanger", "Richard Robitaille", "Atul S Deshmukh", "Julien Ochala"], "journal": "Diabetologia", "year": 2025, "abstract": "AIMS/HYPOTHESIS: Disrupted energy balance is critical for the onset and development of type 2 diabetes mellitus. Understanding of the exact underlying metabolic mechanisms remains incomplete, but skeletal muscle is thought to play an important pathogenic role. As the super-relaxed state of its most abundant protein, myosin, regulates cellular energetics, we aimed to investigate whether it is altered in individuals with type 2 diabetes.\nMETHODS: We used vastus lateralis biopsy specimens (obtained from patients with type 2 diabetes and control participants with similar characteristics), and ran a combination of structural and functional assays consisting of loaded 2'- (or 3')-O-(N-methylanthraniloyl)-ATP (Mant-ATP) chase experiments, x-ray diffraction and LC-MS/MS proteomics in isolated muscle fibres.\nRESULTS: Our studies revealed a greater muscle myosin super-relaxation and decreased ATP demand in male participants with type 2 diabetes than in control participants. Subsequent proteomic analyses indicated that these (mal)adaptations probably originated from remodelled sarcomeric proteins and greater myosin glycation levels in patients than in control participants.\nCONCLUSIONS/INTERPRETATION: Overall, our findings indicate a complex molecular dysregulation of myosin super-relaxed state and energy consumption in male participants with type 2 diabetes. Ultimately, pharmacological targeting of myosin could benefit skeletal muscle and whole-body metabolic health through enhancement of ATP consumption.\nDATA AVAILABILITY: The raw MS data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD053022.", "claims": [{"id": "claim-method", "statement": "An unpaired Student’s t test was used to calculate statistical significance of the differences among the mean values.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40295335", "locator": "sections[15] \"Participants with type 2 diabetes have higher levels of myosin SRX/OFF state in type I muscle fibres\" paragraph 2", "quote": "An unpaired Student’s t test was used to calculate statistical significance of the differences among the mean values."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The raw MS data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD053022 [56]. 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