PXD046755-1

PXD046755 is an original dataset announced via ProteomeXchange.

Title	Insulin and Exercise-induced Phosphoproteomics of Human Skeletal Muscle Identify REPS1 as a New Regulator of Muscle Glucose Uptake
Description	Skeletal muscle regulates glucose uptake in response to insulin and exercise which is critical for maintaining metabolic health. We conducted a comprehensive phosphoproteomic analysis of skeletal muscle from healthy people in response to an acute bout of exercise or insulin stimulation by a hyperinsulinaemic euglycaemic clamp. Our analysis revealed 233 phosphosites regulated by both exercise and insulin of which most phosphosites were regulated in opposite directions. However, 71 phosphosites on 55 proteins displayed regulation in the same direction, indicating a potential convergence of signaling pathways. We identified the vesicle-associated protein, REPS1, to be phosphorylated at Ser709 in response to both insulin and exercise. REPS1 protein level and S709 phosphorylation were closely related to insulin-stimulated glucose uptake in skeletal muscle and required for maximal insulin-stimulated glucose uptake. Furthermore, we observed that insulin triggered phosphorylation of REPS1 Ser709 via P90S6 kinase (RSK) and is impaired in mice and humans with insulin resistance. Collectively, REPS1 is a convergence point for insulin and exercise signaling and a promising therapeutic target in insulin resistance.
HostingRepository	PRIDE
AnnounceDate	2025-06-06
AnnouncementXML	Submission_2025-06-06_13:06:19.374.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jeppe Kjærgaard
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Orbitrap Eclipse; timsTOF Pro 2

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-07 12:22:17	ID requested
⏵ 1	2025-06-06 13:06:19	announced

10.1016/J.XCRM.2025.102163;

submitter keyword: Skeletal muscle signaling, glucose metabolism, phosphoproteomics

Deshmukh lab
contact affiliation	Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen
contact email	atul.deshmukh@sund.ku.dk
lab head
Jeppe Kjærgaard
contact affiliation	Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen
contact email	jeppe.larsen@sund.ku.dk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD046755
     1. Label: PRIDE project
     2. Name: Insulin and Exercise-induced Phosphoproteomics of Human Skeletal Muscle Identify REPS1 as a New Regulator of Muscle Glucose Uptake