ReferenceID 1515
IRS-2/Akt/GSK-3 β/Nrf2 Pathway Contributes to the Protective Effects of Chikusetsu Saponin IVa against Lipotoxicity
Oxid Med Cell Longev
Chronic hyperlipidemia leads to pancreatic beta-cell apoptosis and dysfunction through inducing oxidative stress. Chikusetsu saponin IVa (CHS) showed antioxidant and antidiabetic properties in our previous studies; howev
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- Reference Id
- 1515
- Evidence Id
- 18105
- Core Evidence Id
- 18105
- Source Reference Id
- 3037
- Herb2 Reference Id
- HBREF003834
- Subject Paper Key
- HBIN020306_33884100
- Pubmed Id
- 33884100
- Doi
- 10.1155/2021/8832318
- Paper Title
- IRS-2/Akt/GSK-3 β/Nrf2 Pathway Contributes to the Protective Effects of Chikusetsu Saponin IVa against Lipotoxicity
- Paper Abstract
- Chronic hyperlipidemia leads to pancreatic beta-cell apoptosis and dysfunction through inducing oxidative stress. Chikusetsu saponin IVa (CHS) showed antioxidant and antidiabetic properties in our previous studies; however, its protective effects against lipotoxicity-induced beta-cell oxidative stress and dysfunction are not clear. This study was designed to investigate the effects of CHS against lipotoxicity-induced beta-cell injuries and its possible mechanism involved. High-fat (HF) diet and a low dose of streptozotocin- (STZ-) induced type 2 diabetes mellitus (T2DM) model in vivo and betaTC3 cells subjected to 0.5 mM palmitate (PA) to imitate the lipotoxic model in vitro were performed. Pancreatic functions, ROS, and antioxidant protein measurements were performed to evaluate the effects of CHS on cell injuries. Protein expression levels were measured by Western blotting. Furthermore, siRNA-targeted Nrf2, PI3K/Akt inhibitor (LY294002), or GSK-3beta inhibitor (LiCl) was used to investigate the crosstalk relationships between proteins. As the results showed, CHS treatment inhibited apoptosis, promoted insulin release, and reduced oxidative stress. CHS treatment significantly increased the expression of Nrf2 in the cytoplasm and nuclear protein. The antioxidative and benefit effects of CHS were inhibited by siNrf2. The phosphorylation of IRS-2, PI3K, Akt, and GSK-3beta was markedly increased by CHS which were inhibited by PA. In addition, inhibition of PI3K/Akt or GSK-3beta with specific inhibitors dramatically abrogated the protective effects of CHS, revealing that the IRS-2/Akt/GSK-3beta signaling axis was involved in the protective effects of CHS. These results demonstrate that CHS protected betaTC3 cells against PA-induced oxidative stress and cell dysfunction through Nrf2 by the IRS-2/Akt/GSK-3beta-mediated pathway.
- Journal
- Oxid Med Cell Longev
- Publish Year
- 2021
- Experiment Subject
- Experiment Type
- Cell Experiment
- Phenotype Related
- Beta-cell Injuries; Type 2 Diabetes Mellitus; Chronic Hyperlipidemia
- Paper Title Cn
- Paper Title En
- IRS-2/Akt/GSK-3 β/Nrf2 Pathway Contributes to the Protective Effects of Chikusetsu Saponin IVa against Lipotoxicity
- Bilingual Status
- semi_complete