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.
View: Text | PDF
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

×

Figure 6

Effect of human lean and obese AT-derived EVs in human EndoC-βH3 β cells.

Options: View larger image (or click on image) Download as PowerPoint
Effect of human lean and obese AT-derived EVs in human EndoC-βH3 β cells...
(A) Representative fluorescence microscopy micrographs showing subcutaneous AT–derived EV (SAT-EV) internalization in EndoC-βH3 cells, incubated at the indicated times with SAT-EVs unlabeled (Control) or labeled with PKH26 (red dye) (scale bar: 10 μm). SAT-EV internalization (24 hours) in cells untreated or preincubated for 1 hour with CD29 antibody. Nuclei were stained blue with DAPI (scale bar: 10 μm). (B) Cell survival (MTT) in β cells untreated (control [c]) or treated for 24 hours with lean sAd-EVs (10 × 103/cell) or EVs from lean subcutaneous differentiated adipocytes pretreated with TNF-α/IFN-γ/IL-1β (50, 25, and 2.5 ng/mL, respectively) (sCK-EVs). (C) Cell survival in β cells untreated or treated with sAd-EVs or sCK-EVs, then with TNF-α/IFN-γ/IL-1β (CK) (20, 20, and 1 ng/mL, respectively) 24 hours (mean ± SEM). *P < 0.05, **P < 0.01 vs. c (B) or vs. CK (C); ##P < 0.01 (n = 5), 1-way ANOVA and Tukey’s post hoc test. (D) Insulin secretion (ELISA) in β cells incubated for 1 hour with indicated concentrations of glucose with or without sAd-EVs (mean ± SEM). *P < 0.05, Student’s 2-tailed t test (n = 3). Real-time PCR for TNFA (E), IFNG (F), and IL1B (G) in cells untreated or treated with sAd-EVs or sCK-EVs (mean ± SEM). *P < 0.05, **P < 0.01 vs. c; #P < 0.05, 1-way ANOVA and Tukey’s post hoc test (n = 3). Cell survival in β cells cultured in normal medium (H) or treated with CKs (as for C) (I), and with EVs from obese subcutaneous AT (SAT-EVs) or obese omental AT (OAT-EVs) (10 × 103/cell) (mean ± SEM). * P < 0.05, **P < 0.01, **P < 0.001 vs. c (H) or vs. CK (I), 1-way ANOVA and Tukey’s post hoc test (n = 8). (J) Insulin secretion (ELISA) in EndoC-βH3 cells incubated as in D in the absence or presence of SAT-EVs or OAT-EVs (10 × 103/cell) (mean ± SEM). *P < 0.05, Student’s 2-tailed t test (n = 3). Real-time PCR for TNFA (K), IFNG (L), and IL1B (M) mRNA in cells untreated or treated with lean or obese SAT-EVs 24 hours (mean ± SEM). *P < 0.05, ***P < 0.001 vs. c; ##P < 0.01, 1-way ANOVA and Tukey’s post hoc test (n = 3).