Abstract
Type 1 diabetes is a chronic autoimmune disease affecting nearly 35 million people. This disease develops as T-cells continually attack the β-cells of the islets of Langerhans in the pancreas, which leads to β-cell death, and steadily decreasing secretion of insulin. Lowered levels of insulin minimize the uptake of glucose into cells, thus putting the body in a hyperglycemic state. Despite significant progress in the understanding of the pathophysiology of this disease, there is a need for novel developments in the diagnostics and management of type 1 diabetes. Extracellular vesicles (EVs) are lipid-bound nanoparticles that contain diverse content from their cell of origin and can be used as a biomarker for both the onset of diabetes and transplantation rejection. Furthermore, vesicles can be loaded with therapeutic cargo and delivered in conjunction with a transplant to increase cell survival and long-term outcomes. Crucially, several studies have linked EVs and their cargos to the progression of type 1 diabetes. As a result, gaining a better understanding of EVs would help researchers better comprehend the utility of EVs in regulating and understanding type 1 diabetes. EVs are a composition of biologically active components such as nucleic acids, proteins, metabolites, and lipids that can be transported to particular cells/tissues through the blood system. Through their varied content, EVs can serve as a flexible aid in the diagnosis and management of type 1 diabetes. In this review, we provide an overview of existing knowledge about EVs. We also cover the role of EVs in the pathogenesis, detection, and treatment of type 1 diabetes and the function of EVs in pancreas and islet β-cell transplantation.
Highlights
Extracellular vesicles (EVs) are heterogeneous, ranging from 30 nm to 10 μm in diameter and encompass several types of vesicles, including but not limited to apoptotic bodies, which are large vesicles released from cells undergoing apoptosis; microvesicles, which are released from an evagination of the plasma membrane; and exosomes, which are formed in multivesicular bodies (MVBs), that fuse with the plasma membrane to release the vesicles into the extracellular fluid (Figure 1B, Table 1) [10,12,21,22]
Insulin is the vital gatekeeper in this process, regulating blood glucose levels by triggering cells to take up glucose from the blood (Figure 2A) [41–43]
When researchers first began investigating the causes of type 1 diabetes mellitus (T1DM), genetic risk factors were focused on as the sole trigger, as susceptibility to developing T1DM is influenced by carrying specific high-risk haplotypes of class II human leukocyte antigens (HLA), such as HLA-DR (DR3/4) and HLA-DQ (DQ8) [4,52,53]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. T1DM accounts for the remaining 10% of diabetes cases and is caused by the immunemediated T-cell attack on insulin-producing β-cells in the pancreatic islets. This produces a deficiency in insulin, hyperglycemia (high glucose levels), and changes to the metabolism of proteins and lipids [1]. One potential option in the management of T1DM is the use of EVs. EVs are a heterogeneous population of membranous vesicles secreted from diverse cells that have assorted cargoes such as proteins, lipids, and RNAs that are representative of their parent cells. This review covers current solutions in the treatment of T1DM, with a focus on pancreatic and islet transplantation and the potential benefits of EVs in T1DM diagnosis and management
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