Human Mesenchymal Stem Cell Derived Exosomes Alleviate Type 2 Diabetes Mellitus by Reversing Peripheral Insulin Resistance and Relieving β-Cell Destruction
Human Mesenchymal Stem Cell Derived Exosomes Alleviate Type 2 Diabetes Mellitus by Reversing Peripheral Insulin Resistance and Relieving β-Cell Destruction
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人骨髓间充质干细胞来源的外泌体通过逆转外周胰岛素抵抗及减轻β细胞破坏来缓解2型糖尿病
DOI：
10.1021/acsnano.7b07643
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发表时间：
2018-08-01
期刊：
影响因子：
17.1
通讯作者：
Qian, Hui
中科院分区：
文献类型：
--
作者：
Sun, Yaoxiang;Shi, Hui;Qian, Hui
外泌体是一种纳米级的细胞外囊泡，与间充质干细胞（MSC）一样，在组织再生和损伤修复方面显示出巨大的潜力。MSC在动物模型和临床试验中都显示出缓解糖尿病（DM）。在这项研究中，我们的目的是调查是否来自人脐带MSC（hucMSC-ex）的外泌体对2型糖尿病（T2 DM）有治疗作用。我们采用高脂饮食和链脲佐菌素（STZ）建立了T2 DM大鼠模型。我们发现，静脉注射hucMSC-ex降低血糖水平作为MSC的主要旁分泌途径。HucMSC-ex部分逆转T2 DM患者的胰岛素抵抗，间接促进糖代谢。HucMSC-ex恢复了T2 DM中胰岛素受体底物1和蛋白激酶B的磷酸化（酪氨酸位点），促进了肌肉中葡萄糖转运蛋白4的表达和膜转位，并增加了肝脏中糖原的储存，以维持葡萄糖稳态。HucMSC-ex可抑制STZ诱导的β细胞凋亡，恢复T2 DM的胰岛素分泌功能。总之，来自hucMSC的外泌体可以通过逆转外周胰岛素抵抗和减轻β细胞破坏来缓解T2 DM，为T2 DM治疗提供了替代方法。
Exosomes are nanosized extracellular vesicles (EVs) that show great promise in tissue regeneration and injury repair as mesenchymal stem cell (MSC). MSC has been shown to alleviate diabetes mellitus (DM) in both animal models and clinical trials. In this study, we aimed to investigate whether exosomes from human umbilical cord MSC (hucMSC-ex) have a therapeutic effect on type 2 DM (T2DM). We established a rat model of T2DM using a high-fat diet and streptozotocin (STZ). We found that the intravenous injection of hucMSC-ex reduced blood glucose levels as a main paracrine approach of MSC. HucMSC-ex partially reversed insulin resistance in T2DM indirectly to accelerate glucose metabolism. HucMSC-ex restored the phosphorylation (tyrosine site) of the insulin receptor substrate 1 and protein kinase B in T2DM, promoted expression and membrane trans location of glucose transporter 4 in muscle, and increased storage of glycogen in the liver to maintain glucose homeostasis. HucMSC-ex inhibited STZ-induced beta-cell apoptosis to restore the insulin-secreting function of T2DM. Taken together, exosomes from hucMSC can alleviate T2DM by reversing peripheral insulin resistance and relieving beta-cell destruction, providing an alternative approach for T2DM treatment.