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Adipocyte-derived extracellular vesicles increase insulin secretion through transport of insulinotropic protein cargo.
Nat. Commun. 14:709 (2023)
Adipocyte-derived extracellular vesicles (AdEVs) are membranous nanoparticles that convey communication from adipose tissue to other organs. Here, to delineate their role as messengers with glucoregulatory nature, we paired fluorescence AdEV-tracing and SILAC-labeling with (phospho)proteomics, and revealed that AdEVs transfer functional insulinotropic protein cargo into pancreatic β-cells. Upon transfer, AdEV proteins were subjects for phosphorylation, augmented insulinotropic GPCR/cAMP/PKA signaling by increasing total protein abundances and phosphosite dynamics, and ultimately enhanced 1st-phase glucose-stimulated insulin secretion (GSIS) in murine islets. Notably, insulinotropic effects were restricted to AdEVs isolated from obese and insulin resistant, but not lean mice, which was consistent with differential protein loads and AdEV luminal morphologies. Likewise, in vivo pre-treatment with AdEVs from obese but not lean mice amplified insulin secretion and glucose tolerance in mice. This data suggests that secreted AdEVs can inform pancreatic β-cells about insulin resistance in adipose tissue in order to amplify GSIS in times of increased insulin demand.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Skeletal-muscle; Adipose-tissue; Obesity; Expression; Inflammation; Resistance; Receptor; Mirnas
ISSN (print) / ISBN
2041-1723
e-ISSN
2041-1723
Journal
Nature Communications
Quellenangaben
Volume: 14,
Issue: 1,
Article Number: 709
Publisher
Nature Publishing Group
Publishing Place
London
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Diabetes and Obesity (IDO)
Institute of Biological and Medical Imaging (IBMI)
Institute of Diabetes and Regeneration Research (IDR)
CF Metabolomics & Proteomics (CF-MPC)
Helmholtz Pioneer Campus (HPC)
Institute of Biological and Medical Imaging (IBMI)
Institute of Diabetes and Regeneration Research (IDR)
CF Metabolomics & Proteomics (CF-MPC)
Helmholtz Pioneer Campus (HPC)
Grants
Helmholtz Zentrum Munchen (Helmholtz Developmental Project Grant)
German Research Foundation (DFG)
DFG
German Research Foundation
European Research Council (ERC, CoG Trusted)
Helmholtz-Israel-Cooperation in Personalized Medicine
European Research Council (ERC, CoG Yoyo-LepReSens)
Helmholtz Zentrum Munchen (Helmholtz Portfolio Grant)
Else Kroner-Fresenius-Foundation
ERC (AdG HypoFlam)
Alexander von Humboldt Foundation
Helmholtz Alliance ICEMED by Helmholtz Association
Helmholtz Initiative on Personalized Medicine iMed by Helmholtz Association
Helmholtz cross-program topic "Metabolic Dysfunction"
University of Augsburg
European Research Council (ERC, PREMSOT)
German Research Foundation (DFG)
DFG
German Research Foundation
European Research Council (ERC, CoG Trusted)
Helmholtz-Israel-Cooperation in Personalized Medicine
European Research Council (ERC, CoG Yoyo-LepReSens)
Helmholtz Zentrum Munchen (Helmholtz Portfolio Grant)
Else Kroner-Fresenius-Foundation
ERC (AdG HypoFlam)
Alexander von Humboldt Foundation
Helmholtz Alliance ICEMED by Helmholtz Association
Helmholtz Initiative on Personalized Medicine iMed by Helmholtz Association
Helmholtz cross-program topic "Metabolic Dysfunction"
University of Augsburg
European Research Council (ERC, PREMSOT)