Extracellular Vesicles in β Cell Biology: Role of Lipids in Vesicle Biogenesis, Cargo, and Intercellular Signaling

Authors

Rebecca S Aguirre
Abhishek Kulkarni
Matthew W Becker
Xiaoyong Lei
Soumyadeep Sarkar
Sasanka Ramanadham
Edward A Phelps
Ernesto S Nakayasu
Emily K Sims
Raghavendra G Mirmira

Publication Date

9-1-2022

Journal

Molecular Metabolism

DOI

10.1016/j.molmet.2022.101545

PMID

35817393

PMCID

PMC9294332

PubMedCentral® Posted Date

7-8-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Cell Communication, Cytokines, Diabetes Mellitus, Type 1, Extracellular Vesicles, Humans, Lipids, Islet, Diabetes, Extracellular vesicles

Abstract

BACKGROUND: Type 1 diabetes (T1D) is a complex autoimmune disorder whose pathogenesis involves an intricate interplay between β cells of the pancreatic islet, other islet cells, and cells of the immune system. Direct intercellular communication within the islet occurs via cell surface proteins and indirect intercellular communication has traditionally been seen as occurring via secreted proteins (e.g., endocrine hormones and cytokines). However, recent literature suggests that extracellular vesicles (EVs) secreted by β cells constitute an additional and biologically important mechanism for transmitting signals to within the islet.

SCOPE OF REVIEW: This review summarizes the general mechanisms of EV formation, with a particular focus on how lipids and lipid signaling pathways influence their formation and cargo. We review the implications of EV release from β cells for T1D pathogenesis, how EVs and their cargo might be leveraged as biomarkers of this process, and how EVs might be engineered as a therapeutic candidate to counter T1D outcomes.

MAJOR CONCLUSIONS: Islet β cells have been viewed as initiators and propagators of the cellular circuit giving rise to autoimmunity in T1D. In this context, emerging literature suggests that EVs may represent a conduit for communication that holds more comprehensive messaging about the β cells from which they arise. As the field of EV biology advances, it opens the possibility that intervening with EV formation and cargo loading could be a novel disease-modifying approach in T1D.