The Role of Extracellular Vesicles in β-Cell Function and Viability: A Scoping Review

Abstract

Extracellular vesicles (EVs) released by cells throughout the body have been implicated in diabetes pathogenesis. Understanding the role of EVs in regulation of β-cell function and viability may provide insights into diabetes etiology and may lead to the development of more effective screening and diagnostic tools to detect diabetes earlier and prevent disease progression. This review was conducted to determine what is known from the literature about the effect of EV crosstalk on pancreatic β-cell function and viability in the pathogenesis of diabetes mellitus, to perform a gap analysis for future research directions, and to discuss implications of available evidence for diabetes care. The literature search yielded 380 studies from which 31 studies were determined to meet eligibility criteria. The majority of studies had the disease context of autoimmunity in T1DM. The most commonly studied EV crosstalk dynamics involved localized EV-mediated communication between β-cells and other islet cells, or between β-cells and immune cells. Other organs and tissues secreting EVs that affect β-cells include skeletal muscle, hepatocytes, adipocytes, immune cells, bone marrow, vascular endothelium, and mesenchymal stem cells. Characterization of EV cargo molecules with regulatory effects in β-cells was conducted in 24 studies, with primary focus on microRNA cargo. Gaps identified included scarcity of evidence for the effect on β-cell function and viability of EVs from major metabolic organs/tissues such as muscle, liver, and adipose depots. Future research should address these gaps as well as characterize a broader range of EV cargo molecules and their activity in β-cells.

Multi-Organ Crosstalk with Endocrine Pancreas: A Focus on How Gut Microbiota Shapes Pancreatic Beta-Cells

“…Importantly, different cells from the intestine, such as enterocytes, intestinal epithelial cells, colonocytes, and many others, which are involved in the maintenance of the intestinal barrier, are able to generate exosomes [ 90 , 91 ]. For a better understanding of this topic, a recent review has been published analyzing the effect of different EVs produced by different tissues throughout the body involved in the control of pancreatic beta-cell function [ 16 ]. Then, any change in the microbiome, altering SCFA and EV production, could modify the secretion profile of the colonocytes (or other cell types), affecting the progression of the diseases.…”

“…In agreement, higher levels of circulating EVs are described in both animal models and patients of T2D compared to healthy individuals [ 11 , 15 ]. However, EVs and their bioactive cargo can also significantly affect the capacity of pancreatic beta cells to produce and secrete insulin, or they may also impact beta-cell survival through modulation of proliferative, inflammatory, and apoptotic pathways [ 16 ]. In this complex multi-organ crosstalk, abundant literature highlights the role of gut microbiota-derived metabolites and beta-cell function.…”

Crosstalk Communications Between Islets Cells and Insulin Target Tissue: The Hidden Face of Iceberg

“…Among elements involved in b-cell to b-cell communication, it is well established that EVs play a critical role and can influence b-cell function (28). Indeed, Javeed N et al have recently showed that proinflammatory b-cell EVs induce a complete loss of insulin secretion in response to glucose and promote a pro-inflammatory islet transcriptome (29).…”

Clinical Translational Potentials of Stem Cell-Derived Extracellular Vesicles in Type 1 Diabetes

“…In addition, stem cells have powerful modulation functions for promoting the survival of remaining β cells ( 130 , 131 ). Recently, more evidence has suggested that stem cell-derived EVs have positive effects for promoting the survival of β cells and generation of insulin-producing cells ( 132 , 133 ).…”