PXD064528

PXD064528 is an original dataset announced via ProteomeXchange.

Title	A Cross-Species Subcellular Proteomic Atlas Reveals Pancreatic Islet Cytoarchitecture and Remodeling in Type 2 Diabetes
Description	The unique cytoarchitecture of pancreatic β-cells is key for their role as glucose sensors and endocrine regulators, enabling precise insulin secretion to maintain blood glucose within a narrow physiological range. The dysfunction of β-cells is a hallmark of type 2 diabetes (T2D), yet, despite the clinical importance, the underlying mechanisms remain incompletely understood. To address this, we employed proteomic organelle profiling combined with machine learning–based localization mapping to generate a comprehensive subcellular atlas of pancreatic islets from humans, mice, and pigs. As β-cells are the predominant cell type in islets, the resulting maps primarily reflect β-cell organization and include subcellular and organelle localization data for over 8,000 proteins. Cross-species comparisons revealed conserved features of organelle architecture, previously uncharacterized insulin granule proteins, and species-specific differences in key pathways relevant to β-cell function. Using a T2D mouse model, we further investigated disease-related alterations in β-cell organization. We identified novel insulin granule proteins and observed a reorganization of phosphoinositide signaling, disruption of vesicular trafficking, disassembly of the insulin granule acidification machinery, and reprogramming of mitochondrial amino acid metabolism. Together, our atlas provides a high-resolution in vivo blueprint of pancreatic islet cell architecture and uncovers key processes contributing to β-cell failure in T2D. Key points • We provide a cross-species pancreatic islet proteomic subcellular atlas • Cytoarchitecture is more conserved in human and pig than mice • Phosphoinositide signaling and vesicular trafficking reorganize in T2D • Insulin granule acidification machinery disassembles in T2D • Mitochondria increase proline synthesis machinery in T2D • NHLRC33 is a conserved yet unknown insulin granule protein
HostingRepository	PRIDE
AnnounceDate	2026-06-30
AnnouncementXML	Submission_2026-06-29_21:18:36.377.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Natalie Krahmer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090; scientific name: Sus scrofa domesticus (domestic pig); NCBI TaxID: NEWT:9825;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-02 13:51:18	ID requested
⏵ 1	2026-06-29 21:18:36	announced

Dataset with its publication pending

submitter keyword: human, db/db, organelle proteome, T2D, mouse,Pancreatic islet, pig

Natalie Krahmer
contact affiliation	Emmy-Noether Research Group Cellular Proteomics and Metabolic Signaling Institute for Diabetes and Obesity Helmholtz Diabetes Center - Munich Germany
contact email	natalie.krahmer@helmholtz-munich.de
lab head
Natalie Krahmer
contact affiliation	Helmholtz Center Munich
contact email	natalie.krahmer@helmholtz-muenchen.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/2026/06/PXD064528

PRIDE project URI

• PRIDE
  1. PXD064528
     1. Label: PRIDE project
     2. Name: A Cross-Species Subcellular Proteomic Atlas Reveals Pancreatic Islet Cytoarchitecture and Remodeling in Type 2 Diabetes