中国病理生理杂志2025，Vol.41Issue(5)：927-936,10.DOI:10.3969/j.issn.1000-4718.2025.05.011
利拉鲁肽通过调控SLC7A11/GPX4通路抑制高糖高脂诱导的小鼠胰岛素瘤MIN6细胞铁死亡
Liraglutide regulates SLC7A11/GPX4 pathway to inhibit ferroptosis of mouse insulinoma MIN6 cells induced by high glucose and high fat
摘要
Abstract
AIM:To investigate the role and mechanism of the glucagon-like peptide-1 receptor agonist lira-glutide(Lira)in regulating ferroptosis of mouse insulinoma MIN6 cells induced by high glucose and high fat.METHODS:The mouse insulinoma MIN6 cells were exposed to 30 mmol/L glucose and 500 μmol/L palmitic acid to establish an islet β cell injury model.On this basis,a ferroptosis inducer erastin,a ferroptosis inhibitor ferrostatin-1(Fer-1),and low and high concentrations of Lira were administered.Cell viability of different treatment groups were detected by CCK-8 assay.The malondialdehyde(MDA)kit was used to determine the changes in intracellular MDA content.The reactive oxygen species(ROS)kit was used to detect the changes in the ROS level of cells.The Fe2+fluorescence probe FerroOrange and mitochondrial membrane potential(JC-1)were used to detect the intracellular Fe2+levels and mitochondrial functions in different treatment groups.The mouse insulin ELISA kit was used to detect the insulin secretion of cells.RT-qPCR was used to detect the changes in the expression levels of key ferroptosis genes and insulin secretion genes in different treat-ment groups.Western blot was used to detect the expression levels of key ferroptosis proteins,glutathione peroxidase 4(GPX4)and solute carrier family 7 member 11(SLC7A11)in different treatment groups.RESULTS:Compared with the cells treated with high glucose and high fat,after treatment with Fer-1 and high-dose Lira,the cell viability,insulin secre-tion of the cells,and mitochondrial membrane potential all increased significantly,the levels of ROS,MDA and Fe2+were decreased(P<0.05).The results of RT-qPCR showed that Fer-1 and high-dose Lira significantly upregulated the expres-sion of genes promoting insulin secretion(P<0.05).The results of Western blot showed that Fer-1 and high-dose Lira sig-nificantly upregulated the expression of ferroptosis-inhibiting proteins GPX4 and SLC7A11(P<0.05).CONCLUSION:Liraglutide inhibits ferroptosis of mouse insulinoma MIN6 cells by regulating the SLC7A11/GPX4 signaling pathway,there-by improving the damage and dysfunction of MIN6 cells induced by high glucose and high fat.关键词
2型糖尿病/铁死亡/利拉鲁肽/SLC7A11/GPX4信号通路/胰岛β细胞Key words
type 2 diabetes mellitus/ferroptosis/liraglutide/SLC7A11/GPX4 signaling pathway/islet beta cells分类
医药卫生引用本文复制引用
吴雅文,温舒,胡鹏超,周珍..利拉鲁肽通过调控SLC7A11/GPX4通路抑制高糖高脂诱导的小鼠胰岛素瘤MIN6细胞铁死亡[J].中国病理生理杂志,2025,41(5):927-936,10.基金项目
湖北省自然科学基金创新发展联合基金资助项目(No.2024AFD059) （No.2024AFD059）
襄阳市科技局项目(No.2021ZD17) （No.2021ZD17）
湖北医药学院附属襄阳市第一人民医院院级项目(No.XYY2021M05) （No.XYY2021M05）
