Wu Fang, Shang Chenxin, Jin Ting, Shi Linhui
Department of Endocrinology, The Affiliated Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou 310016, Zhejiang, China.
Critical Care Unit, Ningbo Medical Center, Lihuili Hospital, Ningbo University, Ningbo, China.
Evid Based Complement Alternat Med. 2023 Feb 21;2023:9428241. doi: 10.1155/2023/9428241. eCollection 2023.
Type 2 diabetes mellitus (T2DM) is a global health issue that lacks effective treatments. Dysfunction and/or death of pancreatic -cells (PBCs) are considered a major cause of T2DM. Therefore, elucidating the mechanisms underlying the death of PBCs might be helpful to develop novel strategies to treat T2DM. Ferroptosis is a newly identified form of cell death that has distinct features. However, knowledge regarding the role of ferroptosis in the death of PBCs remains limited. In the current study, we used high glucose (10 mM) (HG) levels to induce ferroptosis in PBC. We also observed that hispidin, a polyphenol compound that can be isolated from , could attenuate ferroptosis induced by HG in PBCs. Mechanistic investigations showed that hispidin led to the upregulation of miR-15b-5p, which directly inhibits the expression of glutaminase (GLS2) which plays an essential role in the glutamine metabolism. In addition, we found that overexpression of GLS2 could abrogate the protective effect of hispidin against ferroptosis caused by HG in PBCs. Therefore, our study provides novel insights into the mechanisms that regulate the death of PBCs.
2型糖尿病（T2DM）是一个缺乏有效治疗方法的全球性健康问题。胰腺β细胞（PBCs）功能障碍和/或死亡被认为是T2DM的主要原因。因此，阐明PBCs死亡的潜在机制可能有助于开发治疗T2DM的新策略。铁死亡是一种新发现的具有独特特征的细胞死亡形式。然而，关于铁死亡在PBCs死亡中的作用的知识仍然有限。在本研究中，我们使用高糖（10 mM）水平诱导PBCs发生铁死亡。我们还观察到，一种可从[具体来源未给出]中分离出的多酚化合物海胆苷，可以减轻高糖诱导的PBCs铁死亡。机制研究表明，海胆苷导致miR-15b-5p上调，而miR-15b-5p直接抑制在谷氨酰胺代谢中起重要作用的谷氨酰胺酶（GLS2）的表达。此外，我们发现GLS2的过表达可以消除海胆苷对高糖诱导的PBCs铁死亡的保护作用。因此，我们的研究为调节PBCs死亡的机制提供了新的见解。
