Xing Yiqian, He Yuchi, Zhang Yuan, Wang Heting, Peng Sihan, Xie Chunguang, Kang Jian, Liu Ya, Zhang Xiyu
Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China.
First Affiliated Hospital of Army Medical University, Chongqing 400038, China.
Evid Based Complement Alternat Med. 2022 Feb 27;2022:5276832. doi: 10.1155/2022/5276832. eCollection 2022.
Diabetes mellitus (DM) is a chronic noninfectious disease that is mainly featured by pancreatic -cell (-cell) dysfunction and impaired glucose homeostasis. Currently, the pathogenesis of dysfunction of the -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 -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 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 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 -cell pyroptosis by inhibiting NLRP3/GSDMD signaling.
糖尿病（DM）是一种慢性非传染性疾病，主要特征为胰岛β细胞（β细胞）功能障碍和葡萄糖稳态受损。目前，糖尿病中β细胞功能障碍的发病机制仍不清楚，针对该病症的治疗方法也有限。大黄素（EMD）是一种天然蒽醌衍生物，已初步证明具有抗糖尿病作用。然而，大黄素对β细胞的潜在作用机制仍有待阐明。在本研究中，我们探究了大黄素对高糖（50 mM）诱导的INS-1细胞系的保护作用及其潜在机制。当INS-1细胞暴露于高糖环境时，用大黄素（5、10和20 μM）进行处理。通过倒置相差显微镜、qRT-PCR、ELISA和蛋白质免疫印迹法检测大黄素的作用效果。结果表明，大黄素可以减轻高糖诱导的INS-1细胞的形态学变化，抑制白细胞介素-1（IL-1）和乳酸脱氢酶（LDH）释放，并促进胰岛素分泌。此外，大黄素抑制NOD样受体蛋白3（NLRP3）激活和gasdermin D（GSDMD）裂解，以减轻高糖诱导的细胞焦亡。NLRP3过表达逆转了大黄素引起的上述变化。总的来说，我们的研究结果表明，大黄素通过抑制NLRP3/GSDMD信号传导减轻高糖诱导的β细胞焦亡。
