Exosomes as Promising Nanostructures in Diabetes Mellitus: From Insulin Sensitivity to Ameliorating Diabetic Complications

Abstract

Diabetes mellitus (DM) is among the chronic metabolic disorders that its incidence rate has shown an increase in developed and wealthy countries due to lifestyle and obesity. The treatment of DM has always been of interest, and significant effort has been made in this field. Exosomes belong to extracellular vesicles with nanosized features (30-150 nm) that are involved in cell-to-cell communication and preserving homeostasis. The function of exosomes is different based on their cargo, and they may contain lipids, proteins, and nucleic acids. The present review focuses on the application of exosomes in the treatment of DM; both glucose and lipid levels are significantly affected by exosomes, and these nanostructures enhance lipid metabolism and decrease its deposition. Furthermore, exosomes promote glucose metabolism and affect the level of glycolytic enzymes and glucose transporters in DM. Type I DM results from the destruction of β cells in the pancreas, and exosomes can be employed to ameliorate apoptosis and endoplasmic reticulum (ER) stress in these cells. The exosomes have dual functions in mediating insulin resistance/sensitivity, and M1 macrophage-derived exosomes inhibit insulin secretion. The exosomes may contain miRNAs, and by transferring among cells, they can regulate various molecular pathways such as AMPK, PI3K/Akt, and β-catenin to affect DM progression. Noteworthy, exosomes are present in different body fluids such as blood circulation, and they can be employed as biomarkers for the diagnosis of diabetic patients. Future studies should focus on engineering exosomes derived from sources such as mesenchymal stem cells to treat DM as a novel strategy.

Milk Exosomal microRNAs: Postnatal Promoters of β Cell Proliferation but Potential Inducers of β Cell De-Differentiation in Adult Life

“…The consecutive switch to β cells to functional maturity may result from the weaning-related loss of MEX miR signaling [ 36 ]. Our hypothesis is supported by recent observations of bidirectional exosome traffic of β cells communicating with various distant cells and tissues of the body [ 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ]. Exosomal miRs emerged as pivotal regulators in the pathogenesis of diabetes [ 1 , 41 , 51 , 52 , 53 , 505 , 546 ].…”

“…Pancreatic β cells maintain a crosstalk with different exosomes either derived from neighboring islet β cells [ 37 , 38 ], islet macrophages [ 39 , 40 ], T-lymphocytes [ 41 ], or exosomes derived from peripheral cells including adipocytes and adipose-tissue macrophages [ 42 ], muscle cells [ 43 ], placenta cells [ 44 , 45 ], and mesenchymal stem cells [ 46 ]. This supports the concept of exosomal miR-mediated communication between and towards β-cells [ 47 ] ( Figure 1 ).…”

Concise review: Current understanding of extracellular vesicles to treat neuropathic pain

“…As biomarkers for diagnose and treatments, EVs are at an emerging stage of clinical application. EVs mediating intercellular communication trigger immune responses, inflammatory responses, and many other processes (Harrell et al, 2019;Qiu et al, 2021;Ashrafizadeh et al, 2022). Exosomes presenting in biological fluids and carrying specific membrane proteins are internalized by recipient cell through soluble and juxtacrine signaling events, fusion, and receptor/raft-mediated endocytosis, as well as phagocytosis, and regulate multiple physiological and pathological processes (Hu et al, 2020).…”

The Challenges Ahead for Exosomes Treatment for Diabetes Mellitus [Letter]

“…We read with great interest of this study 1 titled “Exosomes as Promising Nanostructures in Diabetes Mellitus: From Insulin Sensitivity to Ameliorating Diabetic Complications”. This narrative review made an integrated scoping view of current advances and perspectives of exosomes in Diabetes Mellitus which will benefit researchers in future studies.…”