RT Journal Article T1 Adipocyte-derived extracellular vesicles regulate survival and function of pancreatic β cells. A1 Gesmundo, Iacopo A1 Pardini, Barbara A1 Gargantini, Eleonora A1 Gamba, Giacomo A1 Birolo, Giovanni A1 Fanciulli, Alessandro A1 Banfi, Dana A1 Congiusta, Noemi A1 Favaro, Enrica A1 Deregibus, Maria Chiara A1 Togliatto, Gabriele A1 Zocaro, Gaia A1 Brizzi, Maria Felice A1 Luque, Raul M A1 Castaño, Justo P A1 Bocchiotti, Maria Alessandra A1 Arolfo, Simone A1 Bruno, Stefania A1 Nano, Rita A1 Morino, Mario A1 Piemonti, Lorenzo A1 Ong, Huy A1 Matullo, Giuseppe A1 Falcon-Perez, Juan M A1 Ghigo, Ezio A1 Camussi, Giovanni A1 Granata, Riccarda K1 Adipose tissue K1 Beta cells K1 Diabetes K1 Metabolism AB Extracellular vesicles (EVs) are implicated in the crosstalk between adipocytes and other metabolic organs, and an altered biological cargo has been observed in EVs from human obese adipose tissue (AT). Yet, the role of adipocyte-derived EVs in pancreatic β cells remains to be determined. Here, we explored the effects of EVs released from adipocytes isolated from both rodents and humans and human AT explants on survival and function of pancreatic β cells and human pancreatic islets. EVs from healthy 3T3-L1 adipocytes increased survival and proliferation and promoted insulin secretion in INS-1E β cells and human pancreatic islets, both those untreated or exposed to cytokines or glucolipotoxicity, whereas EVs from inflamed adipocytes caused β cell death and dysfunction. Human lean adipocyte-derived EVs produced similar beneficial effects, whereas EVs from obese AT explants were harmful for human EndoC-βH3 β cells. We observed differential expression of miRNAs in EVs from healthy and inflamed adipocytes, as well as alteration in signaling pathways and expression of β cell genes, adipokines, and cytokines in recipient β cells. These in vitro results suggest that, depending on the physiopathological state of AT, adipocyte-derived EVs may influence β cell fate and function. PB American Society for Clinical Investigation YR 2021 FD 2021-01-28 LK http://hdl.handle.net/10668/17103 UL http://hdl.handle.net/10668/17103 LA en NO Gesmundo I, Pardini B, Gargantini E, Gamba G, Birolo G, Fanciulli A, et al. Adipocyte-derived extracellular vesicles regulate survival and function of pancreatic β cells. JCI Insight. 2021 Mar 8;6(5):e141962 NO This paper is dedicated to the memory of Giacomo Gamba who passed away on May 23, 2020. We thank Giacomo Datta and Alessandro De Matteis for their contribution to the study. We also thank Univercell-Biosolutions SAS (Toulouse, France) for providing EndoC-βH3 cells. This work was supported by the Italian Ministry of Instruction and Research (PRIN 2010 B5B2NL and PRIN 2015 ZHKFTA_008 to E. Ghigo), University of Turin Grant Ex-60% 2018, and the Beneficentia Stiftung Foundation (to RG). This researchreceived funding specifically dedicated to the Department of Medical Sciences from the Italian Ministry for Education, University and Research (Ministero dell’Istruzione, dell’Università e della Ricerca) under the program “Dipartimenti di Eccellenza 2018–2022” (project no. D15D18000410001). JPC and RML are funded by Junta de Andalucía (CTS-1406, BIO-0139), Ministerio de Ciencia, Innovación y Universidades (BFU2016-80360-R), and Instituto de Salud Carlos III; they also receive funding from the European Union (ERDF/ESF, “Investing in your future,” PI16/00264, CP15/00156, and CIBERobn). CIBER is an initiative of Instituto de Salud Carlos III. DS RISalud RD Apr 8, 2025