PXD065342

PXD065342 is an original dataset announced via ProteomeXchange.

Title	Glucagon secretion requires IDE cilium axis
Description	Hyglucagonemia is a hallmark of diabetes caused by dysregulation of glucagon secretion by pancreatic alpha-cells. Although glucose sensing and insulin signaling are well-established regulators, the pathways governing glucagon secretion are not fully understood. Recent evidences suggest that insulin-degrading enzyme (IDE) regulates glucagon secretion through an unknown pathway. We aimed to ascertain the molecular mechanisms downstream of IDE, directing our efforts toward the relationship between IDE and the primary cilium. IDE was not localized to primary cilium of alpha-cells, but IDE deficiency resulted in impaired ciliogenesis. Consistent with lower levels of the insulin receptor (IR), the counterregulatory effect of insulin on glucagon secretion was reduced in IDE-deficient alpha-cells. Two cellular models of ciliary dysfunction (ARL13B-KD and IFT88-KD) resulted in impaired glucagon secretion, as well as a failure of insulin to suppress glucagon secretion in alpha-cells. Importantly, IDE, ciliary markers (AcTubulin, ARL13B) and IR levels were diminished in conditions of physiological glucagon repression. In conclusion, IDE is a mechanistic link between glucose levels and the primary cilium, which regulates glucagon secretion in alpha-cells.
HostingRepository	PRIDE
AnnounceDate	2026-03-23
AnnouncementXML	Submission_2026-03-22_17:25:15.519.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Carmen Duran
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-23 08:22:47	ID requested
⏵ 1	2026-03-22 17:25:16	announced

10.1186/s10020-026-01428-1;

Casanueva-, Á, lvarez E, Sanz-Gonz, á, lez A, Vilas A, C, á, mara-Torres P, Ravier MA, Eslava-Alcon S, Duran-Ruiz MC, Ram, í, rez CM, Petropoulou PI, Rodriguez-Calvo T, Merino B, Perdomo G, Cozar-Castellano I, Glucagon secretion by pancreatic alpha-cells requires an intact tubulin-cytoskeleton-primary cilium axis. Mol Med, 32(1):(2026) [pubmed]

submitter keyword: insulin-degrading enzyme-primary cilium axis,glucagon

MªCarmen Durán-Ruiz
contact affiliation	University of Cadiz
contact email	maricarmen.duran@gm.uca.es
lab head
Carmen Duran
contact affiliation	University of Cadiz
contact email	maricarmen.duran@gm.uca.es
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/2026/03/PXD065342

PRIDE project URI

• PRIDE
  1. PXD065342
     1. Label: PRIDE project
     2. Name: Glucagon secretion requires IDE cilium axis