Department of Endocrinology, Affiliated Hospital of Chengde Medical University, Chengde, China.
Central Laboratory, Affiliated Hospital of Chengde Medical University, Chengde, China.
Sci Rep. 2023 Jun 9;13(1):9446. doi: 10.1038/s41598-023-36602-6.
In this study, we aimed to determine whether liraglutide could effectively reduce insulin resistance (IR) by regulating Sestrin2 (SESN2) expression in L6 rat skeletal muscle cells by examining its interactions with SESN2, autophagy, and IR. L6 cells were incubated with liraglutide (10-1000 nM) in the presence of palmitate (PA; 0.6 mM), and cell viability was detected using the cell counting kit-8 (CCK-8) assay. IR-related and autophagy-related proteins were detected using western blotting, and IR and autophagy-related genes were analyzed using quantitative real-time polymerase chain reaction. Silencing SESN2 was used to inhibit the activities of SESN2. A reduction in insulin-stimulated glucose uptake was observed in PA-treated L6 cells, confirming IR. Meanwhile, PA decreased the levels of GLUT4 and phosphorylation of Akt and affected SESN2 expression. Further investigation revealed that autophagic activity decreased following PA treatment, but that liraglutide reversed this PA-induced reduction in autophagic activity. Additionally, silencing SESN2 inhibited the ability of liraglutide to up-regulate the expression of IR-related proteins and activate autophagy signals. In summary, the data showed that liraglutide improved PA-induced IR in L6 myotubes by increasing autophagy mediated by SESN2.
在这项研究中，我们旨在通过研究 liraglutide 与 SESN2、自噬和胰岛素抵抗（IR）之间的相互作用，确定其是否可以通过调节 L6 大鼠骨骼肌细胞中的 Sestrin2（SESN2）表达来有效降低胰岛素抵抗（IR）。将 L6 细胞与 liraglutide（10-1000 nM）在棕榈酸（PA；0.6 mM）存在下孵育，并使用细胞计数试剂盒-8（CCK-8）测定法检测细胞活力。使用 Western blot 检测与 IR 和自噬相关的蛋白质，使用定量实时聚合酶链反应分析与 IR 和自噬相关的基因。使用沉默 SESN2 抑制 SESN2 的活性。在 PA 处理的 L6 细胞中观察到胰岛素刺激的葡萄糖摄取减少，证实了 IR。同时，PA 降低了 GLUT4 的水平和 Akt 的磷酸化，并影响了 SESN2 的表达。进一步的研究表明，PA 处理后自噬活性降低，但 liraglutide 逆转了这种 PA 诱导的自噬活性降低。此外，沉默 SESN2 抑制了 liraglutide 上调 IR 相关蛋白表达和激活自噬信号的能力。总之，数据表明，liraglutide 通过增加 SESN2 介导的自噬来改善 L6 肌管中 PA 诱导的 IR。
