PXD034826

PXD034826 is an original dataset announced via ProteomeXchange.

Title	Proteomics analysis for the study of beta cell adaptation to stress in mice deficient for insulin-degrading enzyme (IDE)
Description	Appropriate tuning of protein homeostasis through mobilization of the unfolded protein response (UPR) is key to the capacity of pancreatic beta cells to cope with highly variable demand for insulin synthesis. An efficient UPR ensures a sufficient beta cell mass and secretory output but can also affect beta cell resilience to autoimmune aggression. However, the factors regulating protein homeostasis in the face of metabolic and immune challenges are insufficie tly understood. We examined beta cell adaptation to stress in mice deficient for insulin-degrading enzyme (IDE), a ubiquitous protease with high affinity for insulin, a putative ill-defined role in protein homeostasis, and genetic association with type 2 diabetes. IDE deficiency induces a low-level UPR in both standard and autoimmune non-obese diabetic (NOD) mice, associated with rapamycin-sensitive beta cell proliferation, as well as protection from diabetes in NOD mice. Moreover, in NOD islets, IDE deficiency specifically induces strong upregulation of regenerating islet-derived protein 2, a protein attenuating inflammation and protecting from autoimmunity. Our findings establish a role of IDE in islet cell protein homeostasis, corroborate the link between low-level UPR and proliferation, and identify an anti-inflammatory islet cell response uncovered in the absence of IDE of potential interest in autoimmune diabetes.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:45:20.431.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD034826
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Cerina Chhuon
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF

Revision	Datetime	Status	ChangeLog Entry
0	2022-06-22 02:09:19	ID requested
1	2024-06-15 23:22:10	announced
⏵ 2	2024-10-22 06:45:25	announced	2024-10-22: Updated project metadata.

Zhu S, Waeckel-, É, n, é, e E, Oshima M, Moser A, Bessard MA, Gdoura A, Roger K, Mode N, Lipecka J, Yilmaz A, Bertocci B, Diana J, Saintpierre B, Guerrera IC, Scharfmann R, Francesconi S, Mauvais FX, van Endert P, Islet cell stress induced by insulin-degrading enzyme deficiency promotes regeneration and protection from autoimmune diabetes. iScience, 27(6):109929(2024) [pubmed]

10.1016/j.isci.2024.109929;

10.6019/PXD034826;

submitter keyword: LC-MS/MS, proteomics, protein homeostasis, glucose metabolism, unfolded protein response, autoimmunity, diabetes

Ida Chiara Guerrera
contact affiliation	Lab Head of Necker Proteomics Platform
contact email	chiara.guerrera@inserm.fr
lab head
Cerina Chhuon
contact affiliation	Proteomics Platform Necker, PPN-3P5, Structure Fédérative de Recherche SFR Necker, Université Paris Descartes, Paris, France
contact email	cerina.chhuon@inserm.fr
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/2024/06/PXD034826

PRIDE project URI

• PRIDE
  1. PXD034826
     1. Label: PRIDE project
     2. Name: Proteomics analysis for the study of beta cell adaptation to stress in mice deficient for insulin-degrading enzyme (IDE)