Theranostics 2022; 12(3):1342-1372. doi:10.7150/thno.65778 This issue


Integrative biology of extracellular vesicles in diabetes mellitus and diabetic complications

Jing Liu1#, Yanyan Zhang1,2#, Yan Tian1, Wei Huang3, Nanwei Tong4, Xianghui Fu1✉

1. Division of Endocrinology and Metabolism, National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy and Cancer Center, West China Medical School, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China.
2. Department of Geriatric Medicine, Lanzhou University Secondary Hospital, Lanzhou, Gansu, China.
3. Department and Laboratory of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu, China.
4. Division of Endocrinology and Metabolism, Center for Diabetes and Metabolism Research, Laboratory of Diabetes and Islet Transplantation Research, West China Medical School, West China Hospital, Sichuan University, Chengdu, China.
#Co-first author.

This is an open access article distributed under the terms of the Creative Commons Attribution License ( See for full terms and conditions.
Liu J, Zhang Y, Tian Y, Huang W, Tong N, Fu X. Integrative biology of extracellular vesicles in diabetes mellitus and diabetic complications. Theranostics 2022; 12(3):1342-1372. doi:10.7150/thno.65778. Available from

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Graphic abstract

Diabetes mellitus (DM) is a chronic systemic disease with increasing prevalence globally. An important aspect of diabetic pathogenesis is cellular crosstalk and information exchange between multiple metabolic organs and tissues. In the past decade, increasing evidence suggested that extracellular vesicles (EVs), a class of cell-derived membrane vesicles that transmit information and perform inter-cellular and inter-organ communication, are involved in the pathological changes of insulin resistance (IR), inflammation, and endothelial injury, and implicated in the development of DM and its complications. The biogenesis and cargo sorting machinery dysregulation of EVs may mediate their pathogenic roles under diabetic conditions. Moreover, the biogenesis of EVs, their ubiquitous production by different cells, their function as mediators of inter-organ communication, and their biological features in body fluids have generated great promise as biomarkers and clinical treatments. In this review, we summarize the components of EV generation and sorting machinery and highlight their role in the pathogenesis of DM and associated complications. Furthermore, we discuss the emerging clinical implications of EVs as potential biomarkers and therapeutic strategies for DM and diabetic complications. A better understanding of EVs will deepen our knowledge of the pathophysiology of DM and its complications and offer attractive approaches to improve the prevention, diagnosis, treatment, and prognosis of these disorders.

Keywords: diabetes mellitus, extracellular vesicles, biogenesis, sorting, adipocytes, macrophages, islet, endothelial cells