Gremlin-1 protein is involved in the regulation of lipotoxicity-mediated islet β-cell dysfunction
10.3760/cma.j.cn311282-20240127-00044
- VernacularTitle:骨形态发生拮抗蛋白1参与调控脂毒性介导的胰岛β细胞功能障碍
- Author:
Hongwei CHEN
1
;
Ziyi WEI
;
Ningxin CHEN
;
Yue LIU
;
Tingting HAN
;
Yaomin HU
Author Information
1. 上海交通大学医学院附属仁济医院老年医学科，上海 200000
- Keywords:
Lipotoxicity;
Pancreatic β-cells;
Gremlin-1;
BMP4/Smads signaling pathway
- From:
Chinese Journal of Endocrinology and Metabolism
2024;40(5):407-413
- CountryChina
- Language:Chinese
-
Abstract:
Objective:Exploring the role and mechanism of gremlin-1 in lipotoxicity-mediated pancreatic β-cell dysfunction.Methods:The model of lipid toxicity-mediated pancreatic β-cell dysfunction was constructed using palmitic acid(PA) to treat mouse pancreatic β-cells(MIN6). Initially, to clarify the effects of lipotoxicity on islet β-cells, the cellular lipid deposition and changes in the levels of insulin caused by PA were detected. The effects of PA on gremlin-1 expression and its downstream signaling pathway BMPs/Smads were further investigated using qPCR and Western Blot assay. Subsequently, recombinant mouse gremlin-1 protein and BMP signaling pathway inhibitor LDN193189 were used to intervene the cells to explore the effects of gremlin-1 and its downstream signaling pathway BMPs/Smads on pancreatic islet β-cells.Results:PA could reduce pancreatic β-cell viability and insulin secretion capacity( P<0.05). Meanwhile, PA inhibited the expression and secretion of cell gremlin-1 and upregulated BMP-4 and its downstream Smad-1 and Smad-5( P<0.05). Intervention of cells with recombinant mouse gremlin-1 protein resulted in a significant elevation of insulin secretion and a concomitant decrease in the expression of key molecules in the BMP4/Smads signaling pathway( P<0.05). And inhibition of the BMP4/Smads signaling pathway ameliorated PA-induced pancreatic β-cell dysfunction. Conclusion:Gremlin-1 is involved in the regulation of lipotoxicity-mediated pancreatic islet β-cell dysfunction, and this effect may be associated with activation of BMP4/Smads signaling pathway.
