PXD015430

PXD015430 is an original dataset announced via ProteomeXchange.

Title	A Broad Network of Dysregulated Protein Phosphorylation Underlies Muscle Insulin Resistance in Type 2 Diabetes
Description	Skeletal muscle insulin resistance is the earliest defect in type 2 diabetes (T2D), preceding and predicting disease development. Whether this represents the underlying primary defect in T2D or effects of changes in hormones or circulating metabolites is unknown. To address this question, we have developed a “disease-in-a-dish” model by differentiating iPS cells from T2D patients and controls into myoblasts (iMyo) and studied their function in vitro. We find that T2D iMyos exhibit multiple defects mirroring human disease including altered insulin signaling through the IRS/AKT pathway, decreased insulin-stimulated glucose uptake, and reduced mitochondrial oxidation. In addition, using global phosphoproteomics we find that T2D alters phosphorylation of a large network of targets of mTOR, S6K, PKC and other kinases including proteins involved in regulation of Rho-GTPases, mRNA splicing/processing, vesicular trafficking, gene transcription and chromatin remodeling. This cell-autonomous dysregulated phosphorylation network reveals a new dimension in the mechanism underlying insulin resistance in T2D.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:11:22.694.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ashokkumar Jayavelu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-09-12 06:24:34	ID requested
1	2020-08-26 23:17:45	announced
⏵ 2	2024-10-22 05:11:23	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

curator keyword: Biomedical

submitter keyword: Type 2 Diabetes, IPSCs, Insulin signaling, Phosphoproteome

C. Ronald Kahn
contact affiliation	Section of Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA
contact email	c.ronald.kahn@joslin.harvard.edu
lab head
Ashokkumar Jayavelu
contact affiliation	Dept Proteomics and Signal Transduction, MaxPlanck Institute of Biochemistry
contact email	jayavelu@biochem.mpg.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/08/PXD015430

PRIDE project URI

• PRIDE
  1. PXD015430
     1. Label: PRIDE project
     2. Name: A Broad Network of Dysregulated Protein Phosphorylation Underlies Muscle Insulin Resistance in Type 2 Diabetes