Clinical Potential of Extracellular Vesicles in Type 2 Diabetes

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  Figure 1. The clinical potentials of EVs in T2D and its complications. We showed the clinical potentials of EVs described in our review. First, EVs can influence the pathogenesis of T2D by regulating inflammation, insulin signaling and β cell mass. Second, EVs isolated from various body fluids may have huge potentials to be novel biomarkers of T2D and its complications. Some exosomal cargos altered following different treatments may open new prospects for monitoring the efficacy of therapeutic interventions and favor machinery discovery. The therapeutic potentials of EVs have also been presented. Using EVs or their mimics as suitable drug delivery system and MSC-derived EV-based therapy have been exploited a lot, in addition, some EVs possessed beneficial effects can also serve as potential therapeutic agents for T2D and its complications.

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  Figure 2. Biogenesis of EVs and target cell interactions. Microvesicles are generated by plasma membrane budding. Apoptotic bodies are formed by outward budding of the plasma membrane of apoptotic cells. Exosomes are generated within the cells through the endosomal pathway. The cellular contents form intraluminal vesicles which aggregate to form larger vesicles known as MVBs. Some of these MVBs then fuse with lysosomes to degrade cellular components, whereas others fuse with the membrane and are secreted into the extracellular milieu. Subsequently, these exosomes travel to neighboring and distant organs and impact the cellular function of recipient cells.

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  Figure 3. Roles of EVs in regulating diabetic pathological process. In diabetes, altered EVs carrying nucleic acids and proteins can be internalized by various cell types, such as macrophages, adipocytes, hepatocytes, skeletal muscle cells and pancreatic β cells, mediating intercellular communications. 1) Exosomal cargos (such as Shn protein) were modified in the diabetic model and targeted macrophages via regulating various cytokines (IL-6, IL-1β, TNFα, and NF-кB). Then, these altered pathways modulated inflammatory responses in T2D. 2) Exosomal cargos (such as miR-99b, miR-155, miR-29a, miR-26a, adipokine, and calpain 2 γ-secretase) were modified in the diabetic model and targeted hepatocytes via regulating various cytokines (FGF21, FGF2, PPARγ, PPARδ, p-AKT, IR β-subunit, GSK3β, G6pase, PEPCK). Exosomal cargos (such as miR-155, miR-29a, miR-122, miR-192, miR-27a-3p, miR-27b-3p, and miR-26a) were modified in the diabetic model and targeted adipocytes via regulating various cytokines (PPARγ, PPARδ, p-AKT, 2-deoxyglucose, Cpt1b, Cpt2, and PPARα). Exosomal cargos (such as miR-155, miR-29a, miR-29c, miR-27a, miR-23b, miR-27b, and miR-20b-5p) were modified in the diabetic model and targeted…