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ResearchIn-Press PreviewMetabolism Open Access | 10.1172/jci.insight.141962

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

Iacopo Gesmundo,1 Barbara Pardini,2 Eleonora Gargantini,1 Giacomo Gamba,1 Giovanni Birolo,3 Alessandro Fanciulli,1 Dana Banfi,1 Noemi Congiusta,1 Enrica Favaro,3 Maria Chiara Deregibus,5 Gabriele Togliatto,3 Gaia Zocaro,3 Maria Felice Brizzi,3 Raul M. Luque,6 Justo P. Castaño,6 Maria Alessandra Bocchiotti,7 Simone Arolfo,8 Stefania Bruno,3 Rita Nano,9 Mario Morino,8 Lorenzo Piemonti,9 Huy Ong,11 Giuseppe Matullo,3 Juan M. Falcón-Pérez,12 Ezio Ghigo,3 Giovanni Camussi,3 and Riccarda Granata3

1Division of Endocrinology, University of Turin, Turin, Italy

2Italian Institute of Genomic Medicine, University of Turin, Turin, Italy

3Department of Medical Sciences, University of Turin, Turin, Italy

4Division of Endocrinology, University of Turin, Turin, United States of America

52i3T Business Incubator and Technology Transfer, University of Turin, Turin, Italy

6Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain

7Department of Reconstructive and Aesthetic Plastic Surgery, University of Turin, Turin, Italy

8Department of Surgical Sciences, University of Turin, Turin, Italy

9Diabetes Research Institute, San Raffaele Scientific Institute, Milano, Italy

10Diabetes Research Institute, San Raffaele Scientific Institute, Milan, Italy

11Faculty of Pharmacy, Université de Montreal, Montreal, Canada

12Metabolomic Unit, CIC bioGUNE, Derio, Vizcaya, Spain

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1Division of Endocrinology, University of Turin, Turin, Italy

2Italian Institute of Genomic Medicine, University of Turin, Turin, Italy

3Department of Medical Sciences, University of Turin, Turin, Italy

4Division of Endocrinology, University of Turin, Turin, United States of America

52i3T Business Incubator and Technology Transfer, University of Turin, Turin, Italy

6Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain

7Department of Reconstructive and Aesthetic Plastic Surgery, University of Turin, Turin, Italy

8Department of Surgical Sciences, University of Turin, Turin, Italy

9Diabetes Research Institute, San Raffaele Scientific Institute, Milano, Italy

10Diabetes Research Institute, San Raffaele Scientific Institute, Milan, Italy

11Faculty of Pharmacy, Université de Montreal, Montreal, Canada

12Metabolomic Unit, CIC bioGUNE, Derio, Vizcaya, Spain

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1Division of Endocrinology, University of Turin, Turin, Italy

2Italian Institute of Genomic Medicine, University of Turin, Turin, Italy

3Department of Medical Sciences, University of Turin, Turin, Italy

4Division of Endocrinology, University of Turin, Turin, United States of America

52i3T Business Incubator and Technology Transfer, University of Turin, Turin, Italy

6Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain

7Department of Reconstructive and Aesthetic Plastic Surgery, University of Turin, Turin, Italy

8Department of Surgical Sciences, University of Turin, Turin, Italy

9Diabetes Research Institute, San Raffaele Scientific Institute, Milano, Italy

10Diabetes Research Institute, San Raffaele Scientific Institute, Milan, Italy

11Faculty of Pharmacy, Université de Montreal, Montreal, Canada

12Metabolomic Unit, CIC bioGUNE, Derio, Vizcaya, Spain

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1Division of Endocrinology, University of Turin, Turin, Italy

2Italian Institute of Genomic Medicine, University of Turin, Turin, Italy

3Department of Medical Sciences, University of Turin, Turin, Italy

4Division of Endocrinology, University of Turin, Turin, United States of America

52i3T Business Incubator and Technology Transfer, University of Turin, Turin, Italy

6Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain

7Department of Reconstructive and Aesthetic Plastic Surgery, University of Turin, Turin, Italy

8Department of Surgical Sciences, University of Turin, Turin, Italy

9Diabetes Research Institute, San Raffaele Scientific Institute, Milano, Italy

10Diabetes Research Institute, San Raffaele Scientific Institute, Milan, Italy

11Faculty of Pharmacy, Université de Montreal, Montreal, Canada

12Metabolomic Unit, CIC bioGUNE, Derio, Vizcaya, Spain

Find articles by Gamba, G. in: JCI | PubMed | Google Scholar

1Division of Endocrinology, University of Turin, Turin, Italy

2Italian Institute of Genomic Medicine, University of Turin, Turin, Italy

3Department of Medical Sciences, University of Turin, Turin, Italy

4Division of Endocrinology, University of Turin, Turin, United States of America

52i3T Business Incubator and Technology Transfer, University of Turin, Turin, Italy

6Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain

7Department of Reconstructive and Aesthetic Plastic Surgery, University of Turin, Turin, Italy

8Department of Surgical Sciences, University of Turin, Turin, Italy

9Diabetes Research Institute, San Raffaele Scientific Institute, Milano, Italy

10Diabetes Research Institute, San Raffaele Scientific Institute, Milan, Italy

11Faculty of Pharmacy, Université de Montreal, Montreal, Canada

12Metabolomic Unit, CIC bioGUNE, Derio, Vizcaya, Spain

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1Division of Endocrinology, University of Turin, Turin, Italy

2Italian Institute of Genomic Medicine, University of Turin, Turin, Italy

3Department of Medical Sciences, University of Turin, Turin, Italy

4Division of Endocrinology, University of Turin, Turin, United States of America

52i3T Business Incubator and Technology Transfer, University of Turin, Turin, Italy

6Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain

7Department of Reconstructive and Aesthetic Plastic Surgery, University of Turin, Turin, Italy

8Department of Surgical Sciences, University of Turin, Turin, Italy

9Diabetes Research Institute, San Raffaele Scientific Institute, Milano, Italy

10Diabetes Research Institute, San Raffaele Scientific Institute, Milan, Italy

11Faculty of Pharmacy, Université de Montreal, Montreal, Canada

12Metabolomic Unit, CIC bioGUNE, Derio, Vizcaya, Spain

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1Division of Endocrinology, University of Turin, Turin, Italy

2Italian Institute of Genomic Medicine, University of Turin, Turin, Italy

3Department of Medical Sciences, University of Turin, Turin, Italy

4Division of Endocrinology, University of Turin, Turin, United States of America

52i3T Business Incubator and Technology Transfer, University of Turin, Turin, Italy

6Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain

7Department of Reconstructive and Aesthetic Plastic Surgery, University of Turin, Turin, Italy

8Department of Surgical Sciences, University of Turin, Turin, Italy

9Diabetes Research Institute, San Raffaele Scientific Institute, Milano, Italy

10Diabetes Research Institute, San Raffaele Scientific Institute, Milan, Italy

11Faculty of Pharmacy, Université de Montreal, Montreal, Canada

12Metabolomic Unit, CIC bioGUNE, Derio, Vizcaya, Spain

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1Division of Endocrinology, University of Turin, Turin, Italy

2Italian Institute of Genomic Medicine, University of Turin, Turin, Italy

3Department of Medical Sciences, University of Turin, Turin, Italy

4Division of Endocrinology, University of Turin, Turin, United States of America

52i3T Business Incubator and Technology Transfer, University of Turin, Turin, Italy

6Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain

7Department of Reconstructive and Aesthetic Plastic Surgery, University of Turin, Turin, Italy

8Department of Surgical Sciences, University of Turin, Turin, Italy

9Diabetes Research Institute, San Raffaele Scientific Institute, Milano, Italy

10Diabetes Research Institute, San Raffaele Scientific Institute, Milan, Italy

11Faculty of Pharmacy, Université de Montreal, Montreal, Canada

12Metabolomic Unit, CIC bioGUNE, Derio, Vizcaya, Spain

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1Division of Endocrinology, University of Turin, Turin, Italy

2Italian Institute of Genomic Medicine, University of Turin, Turin, Italy

3Department of Medical Sciences, University of Turin, Turin, Italy

4Division of Endocrinology, University of Turin, Turin, United States of America

52i3T Business Incubator and Technology Transfer, University of Turin, Turin, Italy

6Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain

7Department of Reconstructive and Aesthetic Plastic Surgery, University of Turin, Turin, Italy

8Department of Surgical Sciences, University of Turin, Turin, Italy

9Diabetes Research Institute, San Raffaele Scientific Institute, Milano, Italy

10Diabetes Research Institute, San Raffaele Scientific Institute, Milan, Italy

11Faculty of Pharmacy, Université de Montreal, Montreal, Canada

12Metabolomic Unit, CIC bioGUNE, Derio, Vizcaya, Spain

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1Division of Endocrinology, University of Turin, Turin, Italy

2Italian Institute of Genomic Medicine, University of Turin, Turin, Italy

3Department of Medical Sciences, University of Turin, Turin, Italy

4Division of Endocrinology, University of Turin, Turin, United States of America

52i3T Business Incubator and Technology Transfer, University of Turin, Turin, Italy

6Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain

7Department of Reconstructive and Aesthetic Plastic Surgery, University of Turin, Turin, Italy

8Department of Surgical Sciences, University of Turin, Turin, Italy

9Diabetes Research Institute, San Raffaele Scientific Institute, Milano, Italy

10Diabetes Research Institute, San Raffaele Scientific Institute, Milan, Italy

11Faculty of Pharmacy, Université de Montreal, Montreal, Canada

12Metabolomic Unit, CIC bioGUNE, Derio, Vizcaya, Spain

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1Division of Endocrinology, University of Turin, Turin, Italy

2Italian Institute of Genomic Medicine, University of Turin, Turin, Italy

3Department of Medical Sciences, University of Turin, Turin, Italy

4Division of Endocrinology, University of Turin, Turin, United States of America

52i3T Business Incubator and Technology Transfer, University of Turin, Turin, Italy

6Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain

7Department of Reconstructive and Aesthetic Plastic Surgery, University of Turin, Turin, Italy

8Department of Surgical Sciences, University of Turin, Turin, Italy

9Diabetes Research Institute, San Raffaele Scientific Institute, Milano, Italy

10Diabetes Research Institute, San Raffaele Scientific Institute, Milan, Italy

11Faculty of Pharmacy, Université de Montreal, Montreal, Canada

12Metabolomic Unit, CIC bioGUNE, Derio, Vizcaya, Spain

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1Division of Endocrinology, University of Turin, Turin, Italy

2Italian Institute of Genomic Medicine, University of Turin, Turin, Italy

3Department of Medical Sciences, University of Turin, Turin, Italy

4Division of Endocrinology, University of Turin, Turin, United States of America

52i3T Business Incubator and Technology Transfer, University of Turin, Turin, Italy

6Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain

7Department of Reconstructive and Aesthetic Plastic Surgery, University of Turin, Turin, Italy

8Department of Surgical Sciences, University of Turin, Turin, Italy

9Diabetes Research Institute, San Raffaele Scientific Institute, Milano, Italy

10Diabetes Research Institute, San Raffaele Scientific Institute, Milan, Italy

11Faculty of Pharmacy, Université de Montreal, Montreal, Canada

12Metabolomic Unit, CIC bioGUNE, Derio, Vizcaya, Spain

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1Division of Endocrinology, University of Turin, Turin, Italy

2Italian Institute of Genomic Medicine, University of Turin, Turin, Italy

3Department of Medical Sciences, University of Turin, Turin, Italy

4Division of Endocrinology, University of Turin, Turin, United States of America

52i3T Business Incubator and Technology Transfer, University of Turin, Turin, Italy

6Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain

7Department of Reconstructive and Aesthetic Plastic Surgery, University of Turin, Turin, Italy

8Department of Surgical Sciences, University of Turin, Turin, Italy

9Diabetes Research Institute, San Raffaele Scientific Institute, Milano, Italy

10Diabetes Research Institute, San Raffaele Scientific Institute, Milan, Italy

11Faculty of Pharmacy, Université de Montreal, Montreal, Canada

12Metabolomic Unit, CIC bioGUNE, Derio, Vizcaya, Spain

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1Division of Endocrinology, University of Turin, Turin, Italy

2Italian Institute of Genomic Medicine, University of Turin, Turin, Italy

3Department of Medical Sciences, University of Turin, Turin, Italy

4Division of Endocrinology, University of Turin, Turin, United States of America

52i3T Business Incubator and Technology Transfer, University of Turin, Turin, Italy

6Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain

7Department of Reconstructive and Aesthetic Plastic Surgery, University of Turin, Turin, Italy

8Department of Surgical Sciences, University of Turin, Turin, Italy

9Diabetes Research Institute, San Raffaele Scientific Institute, Milano, Italy

10Diabetes Research Institute, San Raffaele Scientific Institute, Milan, Italy

11Faculty of Pharmacy, Université de Montreal, Montreal, Canada

12Metabolomic Unit, CIC bioGUNE, Derio, Vizcaya, Spain

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1Division of Endocrinology, University of Turin, Turin, Italy

2Italian Institute of Genomic Medicine, University of Turin, Turin, Italy

3Department of Medical Sciences, University of Turin, Turin, Italy

4Division of Endocrinology, University of Turin, Turin, United States of America

52i3T Business Incubator and Technology Transfer, University of Turin, Turin, Italy

6Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain

7Department of Reconstructive and Aesthetic Plastic Surgery, University of Turin, Turin, Italy

8Department of Surgical Sciences, University of Turin, Turin, Italy

9Diabetes Research Institute, San Raffaele Scientific Institute, Milano, Italy

10Diabetes Research Institute, San Raffaele Scientific Institute, Milan, Italy

11Faculty of Pharmacy, Université de Montreal, Montreal, Canada

12Metabolomic Unit, CIC bioGUNE, Derio, Vizcaya, Spain

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1Division of Endocrinology, University of Turin, Turin, Italy

2Italian Institute of Genomic Medicine, University of Turin, Turin, Italy

3Department of Medical Sciences, University of Turin, Turin, Italy

4Division of Endocrinology, University of Turin, Turin, United States of America

52i3T Business Incubator and Technology Transfer, University of Turin, Turin, Italy

6Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain

7Department of Reconstructive and Aesthetic Plastic Surgery, University of Turin, Turin, Italy

8Department of Surgical Sciences, University of Turin, Turin, Italy

9Diabetes Research Institute, San Raffaele Scientific Institute, Milano, Italy

10Diabetes Research Institute, San Raffaele Scientific Institute, Milan, Italy

11Faculty of Pharmacy, Université de Montreal, Montreal, Canada

12Metabolomic Unit, CIC bioGUNE, Derio, Vizcaya, Spain

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1Division of Endocrinology, University of Turin, Turin, Italy

2Italian Institute of Genomic Medicine, University of Turin, Turin, Italy

3Department of Medical Sciences, University of Turin, Turin, Italy

4Division of Endocrinology, University of Turin, Turin, United States of America

52i3T Business Incubator and Technology Transfer, University of Turin, Turin, Italy

6Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain

7Department of Reconstructive and Aesthetic Plastic Surgery, University of Turin, Turin, Italy

8Department of Surgical Sciences, University of Turin, Turin, Italy

9Diabetes Research Institute, San Raffaele Scientific Institute, Milano, Italy

10Diabetes Research Institute, San Raffaele Scientific Institute, Milan, Italy

11Faculty of Pharmacy, Université de Montreal, Montreal, Canada

12Metabolomic Unit, CIC bioGUNE, Derio, Vizcaya, Spain

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1Division of Endocrinology, University of Turin, Turin, Italy

2Italian Institute of Genomic Medicine, University of Turin, Turin, Italy

3Department of Medical Sciences, University of Turin, Turin, Italy

4Division of Endocrinology, University of Turin, Turin, United States of America

52i3T Business Incubator and Technology Transfer, University of Turin, Turin, Italy

6Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain

7Department of Reconstructive and Aesthetic Plastic Surgery, University of Turin, Turin, Italy

8Department of Surgical Sciences, University of Turin, Turin, Italy

9Diabetes Research Institute, San Raffaele Scientific Institute, Milano, Italy

10Diabetes Research Institute, San Raffaele Scientific Institute, Milan, Italy

11Faculty of Pharmacy, Université de Montreal, Montreal, Canada

12Metabolomic Unit, CIC bioGUNE, Derio, Vizcaya, Spain

Find articles by Bruno, S. in: JCI | PubMed | Google Scholar |

1Division of Endocrinology, University of Turin, Turin, Italy

2Italian Institute of Genomic Medicine, University of Turin, Turin, Italy

3Department of Medical Sciences, University of Turin, Turin, Italy

4Division of Endocrinology, University of Turin, Turin, United States of America

52i3T Business Incubator and Technology Transfer, University of Turin, Turin, Italy

6Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain

7Department of Reconstructive and Aesthetic Plastic Surgery, University of Turin, Turin, Italy

8Department of Surgical Sciences, University of Turin, Turin, Italy

9Diabetes Research Institute, San Raffaele Scientific Institute, Milano, Italy

10Diabetes Research Institute, San Raffaele Scientific Institute, Milan, Italy

11Faculty of Pharmacy, Université de Montreal, Montreal, Canada

12Metabolomic Unit, CIC bioGUNE, Derio, Vizcaya, Spain

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1Division of Endocrinology, University of Turin, Turin, Italy

2Italian Institute of Genomic Medicine, University of Turin, Turin, Italy

3Department of Medical Sciences, University of Turin, Turin, Italy

4Division of Endocrinology, University of Turin, Turin, United States of America

52i3T Business Incubator and Technology Transfer, University of Turin, Turin, Italy

6Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain

7Department of Reconstructive and Aesthetic Plastic Surgery, University of Turin, Turin, Italy

8Department of Surgical Sciences, University of Turin, Turin, Italy

9Diabetes Research Institute, San Raffaele Scientific Institute, Milano, Italy

10Diabetes Research Institute, San Raffaele Scientific Institute, Milan, Italy

11Faculty of Pharmacy, Université de Montreal, Montreal, Canada

12Metabolomic Unit, CIC bioGUNE, Derio, Vizcaya, Spain

Find articles by Morino, M. in: JCI | PubMed | Google Scholar

1Division of Endocrinology, University of Turin, Turin, Italy

2Italian Institute of Genomic Medicine, University of Turin, Turin, Italy

3Department of Medical Sciences, University of Turin, Turin, Italy

4Division of Endocrinology, University of Turin, Turin, United States of America

52i3T Business Incubator and Technology Transfer, University of Turin, Turin, Italy

6Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain

7Department of Reconstructive and Aesthetic Plastic Surgery, University of Turin, Turin, Italy

8Department of Surgical Sciences, University of Turin, Turin, Italy

9Diabetes Research Institute, San Raffaele Scientific Institute, Milano, Italy

10Diabetes Research Institute, San Raffaele Scientific Institute, Milan, Italy

11Faculty of Pharmacy, Université de Montreal, Montreal, Canada

12Metabolomic Unit, CIC bioGUNE, Derio, Vizcaya, Spain

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1Division of Endocrinology, University of Turin, Turin, Italy

2Italian Institute of Genomic Medicine, University of Turin, Turin, Italy

3Department of Medical Sciences, University of Turin, Turin, Italy

4Division of Endocrinology, University of Turin, Turin, United States of America

52i3T Business Incubator and Technology Transfer, University of Turin, Turin, Italy

6Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain

7Department of Reconstructive and Aesthetic Plastic Surgery, University of Turin, Turin, Italy

8Department of Surgical Sciences, University of Turin, Turin, Italy

9Diabetes Research Institute, San Raffaele Scientific Institute, Milano, Italy

10Diabetes Research Institute, San Raffaele Scientific Institute, Milan, Italy

11Faculty of Pharmacy, Université de Montreal, Montreal, Canada

12Metabolomic Unit, CIC bioGUNE, Derio, Vizcaya, Spain

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1Division of Endocrinology, University of Turin, Turin, Italy

2Italian Institute of Genomic Medicine, University of Turin, Turin, Italy

3Department of Medical Sciences, University of Turin, Turin, Italy

4Division of Endocrinology, University of Turin, Turin, United States of America

52i3T Business Incubator and Technology Transfer, University of Turin, Turin, Italy

6Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain

7Department of Reconstructive and Aesthetic Plastic Surgery, University of Turin, Turin, Italy

8Department of Surgical Sciences, University of Turin, Turin, Italy

9Diabetes Research Institute, San Raffaele Scientific Institute, Milano, Italy

10Diabetes Research Institute, San Raffaele Scientific Institute, Milan, Italy

11Faculty of Pharmacy, Université de Montreal, Montreal, Canada

12Metabolomic Unit, CIC bioGUNE, Derio, Vizcaya, Spain

Find articles by Matullo, G. in: JCI | PubMed | Google Scholar

1Division of Endocrinology, University of Turin, Turin, Italy

2Italian Institute of Genomic Medicine, University of Turin, Turin, Italy

3Department of Medical Sciences, University of Turin, Turin, Italy

4Division of Endocrinology, University of Turin, Turin, United States of America

52i3T Business Incubator and Technology Transfer, University of Turin, Turin, Italy

6Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain

7Department of Reconstructive and Aesthetic Plastic Surgery, University of Turin, Turin, Italy

8Department of Surgical Sciences, University of Turin, Turin, Italy

9Diabetes Research Institute, San Raffaele Scientific Institute, Milano, Italy

10Diabetes Research Institute, San Raffaele Scientific Institute, Milan, Italy

11Faculty of Pharmacy, Université de Montreal, Montreal, Canada

12Metabolomic Unit, CIC bioGUNE, Derio, Vizcaya, Spain

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1Division of Endocrinology, University of Turin, Turin, Italy

2Italian Institute of Genomic Medicine, University of Turin, Turin, Italy

3Department of Medical Sciences, University of Turin, Turin, Italy

4Division of Endocrinology, University of Turin, Turin, United States of America

52i3T Business Incubator and Technology Transfer, University of Turin, Turin, Italy

6Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain

7Department of Reconstructive and Aesthetic Plastic Surgery, University of Turin, Turin, Italy

8Department of Surgical Sciences, University of Turin, Turin, Italy

9Diabetes Research Institute, San Raffaele Scientific Institute, Milano, Italy

10Diabetes Research Institute, San Raffaele Scientific Institute, Milan, Italy

11Faculty of Pharmacy, Université de Montreal, Montreal, Canada

12Metabolomic Unit, CIC bioGUNE, Derio, Vizcaya, Spain

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1Division of Endocrinology, University of Turin, Turin, Italy

2Italian Institute of Genomic Medicine, University of Turin, Turin, Italy

3Department of Medical Sciences, University of Turin, Turin, Italy

4Division of Endocrinology, University of Turin, Turin, United States of America

52i3T Business Incubator and Technology Transfer, University of Turin, Turin, Italy

6Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain

7Department of Reconstructive and Aesthetic Plastic Surgery, University of Turin, Turin, Italy

8Department of Surgical Sciences, University of Turin, Turin, Italy

9Diabetes Research Institute, San Raffaele Scientific Institute, Milano, Italy

10Diabetes Research Institute, San Raffaele Scientific Institute, Milan, Italy

11Faculty of Pharmacy, Université de Montreal, Montreal, Canada

12Metabolomic Unit, CIC bioGUNE, Derio, Vizcaya, Spain

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1Division of Endocrinology, University of Turin, Turin, Italy

2Italian Institute of Genomic Medicine, University of Turin, Turin, Italy

3Department of Medical Sciences, University of Turin, Turin, Italy

4Division of Endocrinology, University of Turin, Turin, United States of America

52i3T Business Incubator and Technology Transfer, University of Turin, Turin, Italy

6Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain

7Department of Reconstructive and Aesthetic Plastic Surgery, University of Turin, Turin, Italy

8Department of Surgical Sciences, University of Turin, Turin, Italy

9Diabetes Research Institute, San Raffaele Scientific Institute, Milano, Italy

10Diabetes Research Institute, San Raffaele Scientific Institute, Milan, Italy

11Faculty of Pharmacy, Université de Montreal, Montreal, Canada

12Metabolomic Unit, CIC bioGUNE, Derio, Vizcaya, Spain

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Published February 4, 2021 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.141962.
Copyright © 2021, Gesmundo et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published February 4, 2021 - Version history
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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 both rodent and human isolated adipocytes 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 untreated or exposed to cytokines or glucolipotoxicity, while EVs from inflamed adipocytes caused β-cell death and dysfunction. Human lean adipocyte-derived EVs produced similar beneficial effects, while EVs from obese AT explants were harmful for human EndoC-βH3 β-cells. We observed differential expression of microRNAs in EVs from healthy and inflamed adipocytes, as well as alteration in signaling pathways and expression of β-cell genes, adipokines and CKs 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.

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