Exosomes and diabetes

Abstract

Summary Diabetes is a group of metabolic diseases characterized by elevated blood glucose levels that drive the development of life‐threatening complications. Diabetes results from a situation of insufficient insulin action, either by deficient production of the hormone by the pancreas, or by the development of insulin resistance in peripheral tissues such as liver, muscle, or the adipose depots. Communication between organs is thus central to the maintenance of glucose homoeostasis. Recently, several studies are evidencing that small vesicles called exosomes released by, amongst other, the adipose tissue can regulate gene expression in other tissues, hence modulating interorgan crosstalk. Therefore, exosomes participate in the development of diabetes and its associated complications. Their study holds the potential of providing us with novel biomarkers for the early diagnosis and stratification of patients at risk of developing diabetes, hence allowing the timely implementation of more personalized therapies. On the other hand, the molecular dissection of the pathways initiated by exosomes under situations of metabolic stress could help to gain a deeper knowledge of the pathophysiology of diabetes and its associated metabolic diseases.

Emerging Roles of Exosomes in T1DM

“…Emerging evidence has indicated that exosomes, which possess immunoregulatory functions, may participate in the initiation and development of autoimmune diabetes ( Figure 1) (28,44). On the one hand, islet-derived exosomes can activate the immune system and lead to autoimmune responses ( Table 1) (53).…”

“…A study indicated that two miRNAs, miR-106b-5p, and miR-222-3p, contribute to bone morrow transplantation (BMT)-induced beta-cell regeneration in mouse models of insulin-deficient diabetes, which may lead to the development of new therapeutic tools for diabetes (90). In addition to protecting the cargo from enzymatic degradation, the use of exosomes as therapeutic vectors has some other advantages, including (1) the ability to be isolated from patients themselves to avoid an immune rejection response; (2) a widespread distribution due to their liposolubility and ability to cross the intact blood-brain barrier; (3) the ability to be modified to target specific cell types by carrying special surface proteins or receptors; and (4) a relatively long half-life in the body (44,(103)(104)(105).…”

Can Epigenetics of Endothelial Dysfunction Represent the Key to Precision Medicine in Type 2 Diabetes Mellitus?

“…This, together with the availability of experimental procedure for their detection and quantification [174], makes them eligible of becoming non-invasive biomarkers for the early diagnosis of diabetes-associated vascular complications. In this regard evidence is accumulating regarding the role played by exosomes and their bioactive content in the pathophysiology of this disease (see Reference [175] for comprehensive review). Exosomes are small extracellular vesicles that shuttle proteins, miRNAs and other lncRNAs, shielding these molecules from enzymatic degradation and ultimately deliver them to recipient cells, both within the tissues and throughout the entire circulatory system.…”

Does microRNA Perturbation Control the Mechanisms Linking Obesity and Diabetes? Implications for Cardiovascular Risk

“…However, miRNAs exert their biological effect not only at the tissue-specific level but also at the level of peripheral blood. Several studies in humans and rodents supported their role as biomarkers for diabetes and metabolic syndromes due to their increase during glucose intolerance (miR-24, miR-30d, miR-34a, miR-126, miR-146 and miR-148a), disease progression (miR-122, miR-133, miR-210), β-cell injury (miR-375) and inflammation (miR-21-5p) [ 56 , 57 , 58 ]. In addition, distinct circulating miRNA profiles between subjects with obesity and T2D aroused considerable attention given their potential as biomarkers for these diseases.…”