International Journal of Nanomedicine (Mar 2022)
Exosomes as Promising Nanostructures in Diabetes Mellitus: From Insulin Sensitivity to Ameliorating Diabetic Complications
Abstract
Milad Ashrafizadeh,1 Alan Prem Kumar,2,3 Amir Reza Aref,4,5 Ali Zarrabi,6 Ebrahim Mostafavi7,8 1Faculty of Engineering and Natural Sciences, Sabanci University, Tuzla, 34956, Istanbul, Turkey; 2NUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore; 3Cancer Science Institute of Singapore and Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117599, Singapore; 4Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; 5Translational Sciences, Xsphera Biosciences Inc., Boston, MA, 02210, USA; 6Department of Biomedical Engineering, Faculty of Engineering and Natural Sciences, Istinye University, Istanbul, 34396, Turkey; 7Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, 94305, USA; 8Department of Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USACorrespondence: Ebrahim Mostafavi, Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, 94305, USA, Email [email protected]; [email protected] Ali Zarrabi, Department of Biomedical Engineering, Faculty of Engineering and Natural Sciences, Istinye University, Istanbul, 34396, Turkey, Email [email protected]: 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.Keywords: diabetes mellitus, insulin resistance, exosome, glucose uptake, lipid metabolism
