PXD064528-1

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

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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