Adipocyte-derived extracellular vesicles increase insulin secretion through transport of insulinotropic protein cargo

Kulaj, Konxhe and Harger, Alexandra and Bauer, Michaela and Caliskan, Özüm S. and Gupta, Tilak Kumar and Chiang, Dapi Menglin and Milbank, Edward and Reber, Josefine and Karlas, Angelos and Kotzbeck, Petra and Sailer, David N. and Volta, Francesco and Lutter, Dominik and Prakash, Sneha and Merl-Pham, Juliane and Ntziachristos, Vasilis and Hauner, Hans and Pfaffl, Michael W. and Tschöp, Matthias H. and Müller, Timo D. and Hauck, Stefanie M. and Engel, Benjamin D. and Gerdes, Jantje M. and Pfluger, Paul T. and Krahmer, Natalie and Stemmer, Kerstin. (2023) Adipocyte-derived extracellular vesicles increase insulin secretion through transport of insulinotropic protein cargo. Nature Communications, 14 (1). p. 709.

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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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Structural Biology and Biophysics (Engel)
UniBasel Contributors:Engel, Ben D
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing Group
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:29 Aug 2023 09:00
Deposited On:29 Aug 2023 09:00

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