MiR-122 Participates in Oxidative Stress and Apoptosis in STZ-Induced Pancreatic β Cells by Regulating PI3K/AKT Signaling Pathway

Abstract

At present, there are few reports concerning the relationship between miR-122 and diabetes. In addition, the effect of miR-122 on streptozotocin- (STZ-) induced oxidative damage in INS-1 cells remains unclear. The present study aimed to investigate the role and modulatory mechanisms involving miR-122 in diabetes. STZ was used to induce INS-1 cell damage. Reverse transcription-quantitative PCR was used to investigate the expression of miR-122. A TUNEL cell apoptosis detection kit was used to detect apoptosis. Intracellular ROS levels were determined using dichlorofluorescein-diacetate. The activities of insulin secretion, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-px) were measured using ELISA kits. Western blotting was used to measure the expression levels of Bax, Bcl-2, PI3K, p-PI3K, caspase-3 and caspase-9, cleaved-caspase-3 and cleaved-caspase-9, AKT, and p-AKT. Then, LY294002 (LY, PI3K inhibitor) was used to treat INS-1 cells, and oxidative stress and apoptosis were measured. The results showed that STZ-induced inhibitory effects on insulin secretion were mitigated by miR-122 inhibitor, and the activities of SOD, CAT, and GSH-px were also increased. Furthermore, miR-122 inhibitor inhibited apoptosis and oxidative stress in STZ-induced INS-1 cells. Finally, the addition of LY increased insulin levels; reduced the activities of SOD, CAT, and GSH-px; and promoted apoptosis in STZ-induced INS-1 cells. In conclusion, interference with miR-122 can inhibit oxidative stress and apoptosis in STZ-induced INS-1 cells, involving a mechanism of action related to the PI3K/AKT pathway.

Magnesium-L-threonate exhibited a neuroprotective effect against oxidative stress damage in HT22 cells and Alzheimer’s disease mouse model

“…The effects of MgT administration on regulating PI3K/Akt pathway, which was a classical pathway related to cell apoptosis[ 24 ], were also detected. As shown in Figure 4 , Aβ 25-35 -exposed cells showed lower ratios of phosphorylated (p)-PI3K/PI3K and p-Akt/Akt than control cells (both P < 0.001).…”

“…A recent study demonstrated that Rotundifuran-induced ROS production could lead to cell apoptosis via suppressing the PI3K/Akt pathway in the cervical cancer cell model[ 35 ]. Another study also showed that inhibition of apoptosis was correlated with the ROS-mediated PI3K/Akt pathway in a streptozotocin-treated INS-1 cell model[ 24 ]. Based on the above findings, dysregulation of the PI3K/Akt signaling pathway supports the relationship between oxidative stress and apoptosis.…”

Crosstalk between MiRNAs/lncRNAs and PI3K/AKT signaling pathway in diabetes mellitus: Mechanistic and therapeutic perspectives

“…In this manner, disruption of miR-122 can effectively impede apoptosis and oxidative stress in STZ-induced INS-1 cells. This modulation is underpinned by a mechanism intricately associated with the PI3K/AKT pathway [ 72 ].…”

Targeting the PI3K/Akt signaling pathway in pancreatic β‐cells to enhance their survival and function: An emerging therapeutic strategy for type 1 diabetes

“…69 Similarly, overexpression of miR-139-5p negatively regulated the expression levels of protein interacting with C-kinase 1 (PICK1), which normally provides functional protection of β-cells through PI3K/Akt activation. 70 Likewise, although their specific gene targets were not investigated, the inhibition of miR-122 71 or let-7 miRNA 72 resulted in the activation of PI3K/Akt signaling in β-cells, which mediated their protection from STZ-induced destruction in vitro 71,72 and in vivo. 72 Collectively, the aforementioned studies indicate that upregulation of PI3K/Akt signaling through dialogue with various miRNA can exert positive effects on β-cell function and survival, and, as such, these miRNA represent viable therapeutics/targets for the treatment of T1D.…”

“… 69 Similarly, overexpression of miR‐139‐5p negatively regulated the expression levels of protein interacting with C‐kinase 1 (PICK1), which normally provides functional protection of β‐cells through PI3K/Akt activation. 70 Likewise, although their specific gene targets were not investigated, the inhibition of miR‐122 71 or let‐7 miRNA 72 resulted in the activation of PI3K/Akt signaling in β‐cells, which mediated their protection from STZ‐induced destruction in vitro 71 , 72 and in vivo. 72 …”