Exosomes from β-cells alleviated hyperglycemia and enhanced angiogenesis in islets of streptozotocin-induced diabetic mice

Abstract

Purpose

Exosomes are small nanoscale vesicles secreted from cells. Exosome-based therapeutic approaches have been evaluated in treating ischemic diseases. In the present study, we explored the effect of exosomes on streptozotozin (STZ)-induced diabetic mouse and its underlying mechanisms.

Methods

Exosomes were isolated from MIN6 cells. Transmission electron microscopy, dynamic light scattering and Western blot were used to identify the exosomes. STZ was used to establish diabetic or abnormal glucose tolerance mouse model. Histology study and flow cytometry were applied to detect the changes in immune responses.

Results

Transplantation of the exosomes into diabetic mice resulted in a longer median survival time compared with the untreated diabetic mice (P<0.01). Transplantation of the exosomes improved glucose tolerance, increased insulin content and preserved the architectures of islets in mice with abnormal glucose tolerance. Moreover, exosome treatment enhanced the expression of CD31, a marker of endothelial cells, and tended to reduce macrophage infiltration in islets of STZ-treated mice.

Conclusion

Exosomes derived from β-cells play a role in preserving pancreatic islet architecture and its function, and in inducing islet angiogenesis, which implicates that exosome treatment could be a novel therapeutic strategy for diabetes.

Keywords:

• exosomes
• diabetes
• vascular regeneration
• macrophage infiltration

Acknowledgments

The authors thank Xin Niu and Yang Wang from the Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital for technique support. This study was funded by the Shanghai Nature Science Fund (16ZR1425800) and grants from the National Natural Science Foundation (81670707). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Ethical statement

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Abbreviations

AUC, Area Under Curve; FBS, fetal bovine serum; FFA, free fatty acid; IDF, International Diabetes Federation; IPGTT, intraperitoneal glucose tolerance test; STZ, streptozotocin; TEM, Transmission Electron Microscopy; TGF, transforming growth factor; TNF, Tumor Necrosis Factor.

Author contributions

All authors contributed to data analysis, drafting or revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

Shanghai Sixth People’s Hospital has applied for a patent related to the methods described in this study, with Chen Wang, Yun Sun and Weiping Jia as co-inventors. The author reports no other conflicts of interest in this work.