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  • Title: Salidroside protects pancreatic β-cells against pyroptosis by regulating the NLRP3/GSDMD pathway in diabetic conditions.
    Author: Zhou J, Yan S, Guo X, Gao Y, Chen S, Li X, Zhang Y, Wang Q, Zheng T, Chen L.
    Journal: Int Immunopharmacol; 2023 Jan; 114():109543. PubMed ID: 36508922.
    Abstract:
    The NACHT, LRP, and PYD domains-containing protein 3 (NLRP3) inflammasome-evoked chronic inflammation is involved in the pathogenesis of diabetes mellitus (DM), and the NLRP3/gasdermin D (GSDMD)-mediated canonical pathway of pyroptosis leads to the loss of pancreatic β-cells and failure of pancreatic function in DM. A previous study demonstrated that salidroside (SAL) alleviates the pathological hyperplasia of pancreatic β-cells in db/db mice. However, it is not clear whether the NLRP3/GSDMD pathway-mediated pyroptosis can be regulated by SAL. In addition, the action of SAL on pancreatic β-cells in DM remains poorly understood. Thus, this study aimed to investigate the effects and underlying mechanisms of SAL on pancreatic β-cell pyroptosis. Rat insulinoma (INS-1) cells were cultured in a medium containing either high glucose (HG) or HG plus high insulin (HG-HI), and the effects of SAL on cell viability, AMP-activated protein kinase (AMPK) activity, reactive oxygen species (ROS) generation, NLRP3/GSDMD activation, and pyroptotic body formation were assessed. Streptozocin-induced DM mice were used to further investigate the effects of SAL on pancreatic pyroptosis. The results revealed aberrances on cell viability, AMPK activity, ROS generation, NLRP3/GSDMD activation, and pyroptotic body formation in HG- and HG-HI-exposed INS-1 cells; these abnormal effects were corrected by SAL in both a concentration- and AMPK-dependent manner. Moreover, SAL administration activated AMPK, suppressed NLRP3/GSDMD signaling, and protected pancreatic β-cells against pyroptosis in DM mice. These findings suggest that SAL promotes AMPK activation to suppress NLRP3/GSDMD-related pyroptosis in pancreatic β-cells under DM conditions.
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