Minireview: Emerging Roles for Extracellular Vesicles in Diabetes and Related Metabolic Disorders

Abstract

Extracellular vesicles (EVs), membrane-contained vesicles released by most cell types, have attracted a large amount of research interest over the past decade. Because of their ability to transfer cargo via regulated processes, causing functional impacts on recipient cells, these structures may play important roles in cell-cell communication and have implications in the physiology of numerous organ systems. In addition, EVs have been described in most human biofluids and have wide potential as relatively noninvasive biomarkers of various pathologic conditions. Specifically, EVs produced by the pancreatic β-cell have been demonstrated to regulate physiologic and pathologic responses to β-cell stress, including β-cell proliferation and apoptosis. β-Cell EVs are also capable of interacting with immune cells and may contribute to the activation of autoimmune processes that trigger or propagate β-cell inflammation and destruction during the development of diabetes. EVs from adipose tissue have been shown to contribute to the development of the chronic inflammation and insulin resistance associated with obesity and metabolic syndrome via interactions with other adipose, liver, and muscle cells. Circulating EVs may also serve as biomarkers for metabolic derangements and complications associated with diabetes. This minireview describes the properties of EVs in general, followed by a more focused review of the literature describing EVs affecting the β-cell, β-cell autoimmunity, and the development of insulin resistance, which all have the potential to affect development of type 1 or type 2 diabetes.

Figure 1.

EV-related publications over time. A PubMed search was performed for publications in 5-year intervals ranging from 1900 to 2015. Search terms included exosomes OR ectosomes OR “extracellular vesicles” OR microvesicles OR microparticles OR apoptosomes OR “apoptotic bodies.” No manuscripts containing these terms were identified before 1950.

Figure 2.

Current understanding of EV release and target cell interactions. Parent cells release EVs via blebbing from the plasma membrane (PM) or exocytosis of vesicles derived from the multivesicular body. EVs travel to target cells where effects are mediated via interaction with surface receptors, endocytic uptake, or direct PM fusion and transfer of cargo.