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Organelle proteomics of human, neonatal pig, healthy and diabetic mouse islets.

Cell Rep. 45, 117751:117751 (2026)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Pancreatic islets, in which β cells constitute 50%–80% of the endocrine mass, are the body’s site for glucose-regulated insulin secretion. Pancreatic islet dysfunction is a hallmark of type 2 diabetes. Nevertheless, the molecular changes that impair their function remain insufficiently understood. To determine how islet cellular organization supports function and how it deteriorates in disease, we used machine learning-based organelle proteomics to build an organelle atlas of pancreatic islets from mice, humans, and pig neonatal islet-like cells. This cross-species resource maps localization of ∼8,000 proteins, revealing conserved organelle organization and identifying previously unrecognized components of insulin granules. Applying our organelle proteomics workflow to db/db mice, a T2D model uncovered disease-associated changes affecting vesicular trafficking and mitochondrial amino acid metabolism. Additionally, we found a disassembly of the insulin-granule acidification machinery. Our atlas provides insights into islet subcellular organization and identifies processes whose disruption may drive pancreatic islet failure in T2D.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Proteomics ; Organelle ; Proteome ; Diabetes Mellitus ; Shotgun Proteomics ; Islet; Pancreatic Beta-cells; Impaired Insulin-secretion; Mitochondrial Metabolism; High-glucose; Vacuolar H+; Atpase; Stress; Activation; Mechanisms; Platform
ISSN (print) / ISBN 2211-1247
e-ISSN 2211-1247
Journal Cell Reports
Quellenangaben Volume: 45, Issue: 8, Pages: 117751 Article Number: 117751 Supplement: ,
Publisher Elsevier
Publishing Place 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Reviewing status Peer reviewed
Grants DFG Emmy Noether
European Foundation for the Study of Diabetes (Future Leader Award)
International Helmholtz Research School for Diabetes
Helmholtz Association-Initiative and Networking Fund
European Research Council ERC-CoG
German Research Foundation