Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China.
Hebei Key Laboratory of Metabolic Disease, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China.
Mol Med Rep. 2019 Aug;20(2):1230-1240. doi: 10.3892/mmr.2019.10347. Epub 2019 Jun 5.
The expression of microRNA‑802 (miR‑802) is known to be associated with insulin resistance (IR); however, the mechanism remains unclear. The present study investigated how miR‑802 contributes to the development of IR using C57BL/6J mice fed a high‑fat diet (HFD) to establish a model of IR. Adeno‑associated virus overexpressing miR‑802 was administered to the mice via tail vein injection. The effects of miR‑802 on reactive oxygen species (ROS), lipid peroxidation (LPO) and the activities of multiple ROS‑related enzymes were investigated. Western blot analysis was used to estimate the protein levels of extracellular signal regulated kinase (ERK), p38mitogen‑activated protein kinases (p38MAPK), c‑Jun N‑terminal kinase (JNK), insulin receptor substrate 1 (IRS‑1) and protein kinase B (AKT1). The results demonstrated that the levels of ROS and LPO production were increased in the livers of the miR‑802‑treated group compared with the control group. The activities of the ROS‑related enzymes were reduced. Furthermore, the expression of phosphorylated (phosphor)‑p38MAPK and phosphor‑JNK were upregulated in the miR‑802 overexpression group, whereas there was no difference in the expression levels of phosphor‑ERK. The expression levels of phosphor‑AKT1 were reduced in the miR‑802‑treated group and these effects were reversed by miR‑802 knockdown. In conclusion, the results demonstrate that miR‑802 may cause IR by activating the JNK and p38MAPK pathways to increase hepatic oxidative stress.
miR-802 的表达与胰岛素抵抗（IR）有关；然而，其机制尚不清楚。本研究通过用高脂肪饮食（HFD）喂养 C57BL/6J 小鼠建立 IR 模型，探讨了 miR-802 如何导致 IR 的发展。通过尾静脉注射将过表达 miR-802 的腺相关病毒给予小鼠。研究了 miR-802 对活性氧（ROS）、脂质过氧化（LPO）和多种 ROS 相关酶活性的影响。Western blot 分析用于估计细胞外信号调节激酶（ERK）、p38 丝裂原活化蛋白激酶（p38MAPK）、c-Jun N-末端激酶（JNK）、胰岛素受体底物 1（IRS-1）和蛋白激酶 B（AKT1）的蛋白水平。结果表明，与对照组相比，miR-802 处理组的肝脏中 ROS 和 LPO 产生水平增加。ROS 相关酶的活性降低。此外，miR-802 过表达组中磷酸化（phosphor）-p38MAPK 和 phosphor-JNK 的表达上调，而 phosphor-ERK 的表达水平没有差异。miR-802 处理组中 phosphor-AKT1 的表达水平降低，而 miR-802 敲低可逆转这些影响。综上所述，研究结果表明，miR-802 可能通过激活 JNK 和 p38MAPK 通路增加肝氧化应激引起 IR。
