缺氧脂肪细胞和肥胖个体来源的细胞外囊泡降低胰岛素刺激的葡萄糖摄取。

Extracellular Vesicles from Hypoxic Adipocytes and Obese Subjects Reduce Insulin-Stimulated Glucose Uptake.

机构信息

Department of Molecular and Cellular Physiology, Institute of Translational Medicine, The University of Liverpool, Liverpool, UK.

CIC bioGUNE, CIBERehd, Derio, Bizkaia, Spain.

出版信息

Mol Nutr Food Res. 2018 Mar;62(5). doi: 10.1002/mnfr.201700917. Epub 2018 Feb 20.

SCOPE

We investigate the effects of extracellular vesicles (EVs) obtained from in vitro adipocyte cell models and from obese subjects on glucose transport and insulin responsiveness.

METHODS AND RESULTS

EVs are isolated from the culture supernatant of adipocytes cultured under normoxia, hypoxia (1% oxygen), or exposed to macrophage conditioned media (15% v/v). EVs are isolated from the plasma of lean individuals and subjects with obesity. Cultured adipocytes are incubated with EVs and activation of insulin signalling cascades and insulin-stimulated glucose transport are measured. EVs released from hypoxic adipocytes impair insulin-stimulated 2-deoxyglucose uptake and reduce insulin mediated phosphorylation of AKT. Insulin-mediated phosphorylation of extracellular regulated kinases (ERK1/2) is not affected. EVs from individuals with obesity decrease insulin stimulated 2-deoxyglucose uptake in adipocytes (p = 0.0159).

CONCLUSION

EVs released by stressed adipocytes impair insulin action in neighboring adipocytes.

范围

我们研究了体外脂肪细胞模型和肥胖受试者来源的细胞外囊泡（EVs）对葡萄糖转运和胰岛素反应的影响。

方法和结果

EVs 是从常氧、低氧（1%氧气）或巨噬细胞条件培养基（15%v/v）培养的脂肪细胞的培养上清液中分离得到的。EVs 是从瘦个体和肥胖个体的血浆中分离得到的。培养的脂肪细胞与 EVs 孵育，并测量胰岛素信号级联的激活和胰岛素刺激的葡萄糖转运。从低氧脂肪细胞释放的 EVs 损害胰岛素刺激的 2-脱氧葡萄糖摄取，并降低胰岛素介导的 AKT 磷酸化。胰岛素介导的细胞外调节激酶（ERK1/2）的磷酸化不受影响。肥胖个体来源的 EVs 降低了脂肪细胞中胰岛素刺激的 2-脱氧葡萄糖摄取（p = 0.0159）。