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

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

来自β细胞的外泌体减轻了链脲佐菌素诱导的糖尿病小鼠胰岛的高血糖并增强了血管生成

DOI:
10.2147/dmso.s213400
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发表时间:
2019-01-01
期刊:
DIABETES METABOLIC SYNDROME AND OBESITY-TARGETS AND THERAPY
影响因子:
--
通讯作者:
Jia, Weiping
Jia, Weiping
中科院分区:
其他
文献类型:
--
作者:
Sun, Yun;Mao, Qianyun;Jia, Weiping

文献摘要

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目的外泌体是由细胞分泌的小的纳米级囊泡。已经在治疗缺血性疾病中评价了基于外来体的治疗方法。本研究探讨了exosomes对链脲佐菌素(STZ)诱导的糖尿病小鼠的作用及其机制。方法从MIN6细胞中分离外泌体。用透射电镜、动态光散射和Western blot鉴定外泌体。采用链脲佐菌素(STZ)建立糖尿病及糖耐量异常小鼠模型。组织学观察和流式细胞术检测免疫反应的变化。结果糖尿病小鼠移植exosomes后的中位生存时间较未移植组明显延长(P<0.01)。移植外泌体可改善糖耐量异常小鼠的糖耐量,增加胰岛素含量,并保留胰岛结构。此外,外泌体处理增强了内皮细胞标志物CD31的表达,并倾向于减少STZ处理小鼠胰岛中的巨噬细胞浸润。结论β细胞来源的Exosomes具有保护胰岛结构和功能,促进胰岛血管新生的作用,exosomes治疗可能成为糖尿病治疗的新策略。
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.