Adipocyte-derived extracellular vesicles regulate survival and function of pancreatic β cells
Iacopo Gesmundo, … , Giovanni Camussi, Riccarda Granata
Iacopo Gesmundo, … , Giovanni Camussi, Riccarda Granata
Published February 4, 2021
Citation Information: JCI Insight. 2021;6(5):e141962. https://doi.org/10.1172/jci.insight.141962.
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Research Article Metabolism

Adipocyte-derived extracellular vesicles regulate survival and function of pancreatic β cells

Abstract

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.

Authors

Iacopo Gesmundo, Barbara Pardini, Eleonora Gargantini, Giacomo Gamba, Giovanni Birolo, Alessandro Fanciulli, Dana Banfi, Noemi Congiusta, Enrica Favaro, Maria Chiara Deregibus, Gabriele Togliatto, Gaia Zocaro, Maria Felice Brizzi, Raul M. Luque, Justo P. Castaño, Maria Alessandra Bocchiotti, Simone Arolfo, Stefania Bruno, Rita Nano, Mario Morino, Lorenzo Piemonti, Huy Ong, Giuseppe Matullo, Juan M. Falcón-Pérez, Ezio Ghigo, Giovanni Camussi, Riccarda Granata

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Figure 3

Regulation of signaling pathways and expression of β cell genes, adipokines, and CKs in INS-1E β cells treated with Ad-EVs and CK-EVs.

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Regulation of signaling pathways and expression of β cell genes, adipoki...
Representative Western blots for phosphorylated Akt (P-Akt) (A), P-GSK-3β (B), P-ERK1/2 (C), P-PERK (D), P-eIF2α (E), and P-JNK (F) in cells untreated (control [c]) or treated with Ad-EVs or CK-EVs for 24 hours (top). Blots were reprobed with nonphosphorylated antibodies for normalization (bottom). Results are expressed as a percentage of control untreated cells (mean ± SEM). *P < 0.05, **P < 0.01, ***P < 0.001 vs. c; #P < 0.05, ###P < 0.001 by 1-way ANOVA and Tukey’s post hoc test (n = 3). Real-time PCR for the UPR gene Chop (G) and for β cell genes, Pdx1 (H) and Nkx6.1 (I); adipokines: adiponectin (Adipoq) (J), leptin (Lep) (K), and adipsin (Cfd, complement factor D) (L); and CKs: TNF-α (Tnfa) (M), IFN-γ (Ifng) (N), and IL-1β (Il1b) (O) in β cells untreated or treated with Ad-EVs or CK-EVs for 24 hours (mean ± SEM). *P < 0.05, **P < 0.01, ***P < 0.001 vs. c; #P < 0.05, ##P < 0.01, ###P < 0.001 by 1-way ANOVA and Tukey’s post hoc test (n = 3 for G–I and M–O; n = 5 for J–L).