Liraglutide regulates SLC7A11/GPX4 pathway to inhibit ferroptosis of mouse insulinoma MIN6 cells induced by high glucose and high fat
10.3969/j.issn.1000-4718.2025.05.011
- VernacularTitle: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
- Author:
Yawen WU
1
;
Shu WEN
;
Pengchao HU
;
Zhen ZHOU
Author Information
1. 武汉科技大学医学院襄阳市第一人民医院研究生联合培养基地内分泌科,湖北 襄阳 441000
- Publication Type:Journal Article
- Keywords:
type 2 diabetes mellitus;
ferroptosis;
liraglutide;
SLC7A11/GPX4 signaling pathway;
islet beta cells
- From:
Chinese Journal of Pathophysiology
2025;41(5):927-936
- CountryChina
- Language:Chinese
-
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.
