GDF15 plays a critical role in insulin secretion in INS-1 cells and human pancreatic islets

Mounting evidence points to a link between growth differentiation factor-15 (GDF15) expression and the onset and progression of diabetes mellitus. However, the exact role of GDF15 in pancreatic beta-cell function is unclear. To examine the role of GDF15 in beta-cell function, bioinformatics analysis and functional experiments involving GDF15 silencing and overexpression were performed in INS-1 cells and human islets. Public microarray and RNA-seq expression data showed that islets obtained from diabetic donors express high levels of GDF15 compared to islets obtained from normal donors. Moreover, analysis of RNA-seq expression data revealed that GDF15 expression correlates positively with that of insulin (INS), KCNJ11, GLUT1, MAFA, INSR and negatively with that of Glucokinase (GCK) and Alpha-Ketoglutarate Dependent Dioxygenase (FTO). No T2D-associated genetic variants in the GDF15 were found to pass genome-wide significance in the TIGER portal. Expression silencing of Gdf15 in INS-1 cells reduced insulin release, glucose uptake levels, increased reactive oxygen species (ROS) production and apoptosis levels. While Gdf15-silenced cells downregulated mRNA expression of Ins, Pdx1, Mafa, and Glut2 genes, its overexpression human islets was associated with increased insulin secretion and upregulated expression of MAFA and GLUT1 but not INS or GCK. Silencing of Pdx1 or Mafa in INS-1 cells did not affect the expression of GDF15. These findings suggest that GDF15 plays a significant role in pancreatic beta-cell function.

Automated summary

Mounting evidence suggests a link between GDF15 expression and diabetes mellitus. The role of GDF15 in pancreatic beta-cell function was investigated through bioinformatics analysis and functional experiments. Silencing Gdf15 reduced insulin release, glucose uptake, increased ROS production, and apoptosis levels, while its overexpression in human islets was associated with increased insulin secretion. These findings highlight the significant role of GDF15 in pancreatic beta-cell function.