Emodin Alleviates High-Glucose-Induced Pancreatic β -Cell Pyroptosis by Inhibiting NLRP3/GSDMD Signaling.

Diabetes mellitus (DM) is a chronic noninfectious disease that is mainly featured by pancreatic β -cell ( β -cell) dysfunction and impaired glucose homeostasis. Currently, the pathogenesis of dysfunction of the β -cells in DM remains unclear, and therapeutic approaches to it are limited. Emodin (EMD), a natural anthraquinone derivative, has been preliminarily proven to show antidiabetic effects. However, the underlying mechanism of EMD on β -cells still needs to be elucidated. In this study, we investigated the protective effects of EMD on the high glucose (50 mM)-induced INS-1 cell line and the underlying mechanism. INS-1 cells were treated with EMD (5, 10, and 20  μ M) when exposed to high glucose. The effects of EMD were examined by using the inverted phase-contrast microscope, qRT-PCR, ELISA, and western blot. The results showed that EMD could alleviate cellular morphological changes, suppress IL-1 β and LDH release, and promote insulin secretion in high-glucose-induced INS-1 cells. Furthermore, EMD inhibits NOD-like receptor protein 3 (NLRP3) activation and gasdermin D (GSDMD) cleavage to alleviate pyroptosis induced by high glucose. Overexpression of NLRP3 reversed the above changes caused by EMD. Collectively, our findings suggest that EMD attenuates high-glucose-induced β -cell pyroptosis by inhibiting NLRP3/GSDMD signaling.