Injury Factors Alter miRNAs Profiles of Exosomes Derived from Islets and Circulation

Islets damage is a major abnormality underling diabetes, thus timely monitoring islets destruction is critically needed. Recent studies discovered the biological functions of exosomes and suggested the value of exosomes in disease diagnosis and prognosis. This study aimed to investigate the impact of injury factors on the miRNA profiles of islet exosomes and determine whether circulating exosomal miRNAs would be suitable as biomarkers of islets cell damage. Islets were isolated from ICR mice and induced injury in vitro by mixed cytokines (TNFα, IL-1β and IFNγ) and streptozotocin (STZ) and exosomes were derived from the cultural supernatant. Using miRNA microarray analysis, we found 22 and 11 differentially expressed miRNAs in islet exosomes of STZ and cytokines treatment, respectively. 6 differentially expressed exosaml miRNAs were found both in STZ and cytokines treated group, and miR-375-3p and miR-129-5p were validated by quantitative RT-PCR. Serum exosomes were isolated from ICR mice of islets damage in vivo induced by STZ injection and subjects with various glucose metabolism states and diabetic duration. Quantitative RT-PCR demonstrated exosomal miR-375-3p dramatically increased in serum of STZ treated mouse prior to the turbulence of blood glucose and serum insulin. In human serum exosomes, miR-375-3p was elevated in newly new-onset diabetes patients. Overall, our results suggest that injury factors cytokines and STZ affected the miRNA profiles of exosomes derived from islets and exosomal miR-375-3p showed promising potential as a biomarker of islets damage. Further studies were necessary to purify islet-specific exosomes from circulation for improving the accuracy.