2026-04-29T15:25:25Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/268462025-07-24T00:18:05Zcom_20.500.12105_19586com_20.500.12105_2202col_20.500.12105_19587
Repisalud
author
Lewis, Christopher T A
author
Moreno-Justicia, Roger
author
Savoure, Lola
author
Calvo, Enrique
author
Bak, Agata
author
Laitila, Jenni
author
Seaborne, Robert A E
author
Larsen, Steen
author
Iwamoto, Hiroyuki
author
Cefis, Marina
author
Morais, Jose A
author
Gouspillou, Gilles
author
Alegre-Cebollada, Jorge
author
Hawke, Thomas J
author
Vazquez, Jesús
author
Adrover, Miquel
author
Marcangeli, Vincent
author
Hammad, Rami
author
Granet, Jordan
author
Gaudreau, Pierrette
author
Aubertin-Leheudre, Mylène
author
Bélanger, Marc
author
Robitaille, Richard
author
Deshmukh, Atul S
author
Ochala, Julien
funder
Novo Nordisk Foundation
funder
Instituto de Salud Carlos III
funder
Ministerio de Ciencia, Innovación y Universidades (España)
funder
Fundación ProCNIC
funder
Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España)
2025-07-23T14:19:21Z
2025-07-23T14:19:21Z
2025-08
Diabetologia. 2025 Aug;68(8):1836-1850.
Diabetologia
40295335
https://hdl.handle.net/20.500.12105/26846
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. 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. 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. 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. The raw MS data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD053022.
eng
Diabetes
Metabolism
Myosin
Skeletal muscle
Dysregulated skeletal muscle myosin super-relaxation and energetics in male participants with type 2 diabetes mellitus.
research article
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URL
https://repisalud.isciii.es/bitstreams/e9f07dff-1a9a-421a-a8e3-1e36f30a95c8/download
File
MD5
e52278ba0e5d51b09c552a2c8a7cd749
4348765
application/pdf
Dysregulated skeletal muscle myosin_Diabetologia_2025.pdf