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 () expression and the onset and progression of diabetes mellitus. However, the exact role of in pancreatic β-cell function is unclear. To examine the role of in β-cell function, bioinformatics analysis and functional experiments involving 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 compared to islets obtained from normal donors. Moreover, analysis of RNA-seq expression data revealed that expression correlates positively with that of insulin (), , , , and negatively with that of Glucokinase () and Alpha-Ketoglutarate Dependent Dioxygenase (). No T2D-associated genetic variants in the were found to pass genome-wide significance in the TIGER portal. Expression silencing of in INS-1 cells reduced insulin release, glucose uptake levels, increased reactive oxygen species (ROS) production and apoptosis levels. While -silenced cells downregulated mRNA expression of , , , and 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 or in INS-1 cells did not affect the expression of GDF15. These findings suggest that plays a significant role in pancreatic β-cell function.