Background: Diabetes mellitus (DM) is a common complication found in beta-thalassemia patients. The mechanism of DM in beta-thalassemia patients is still unclear, but it could be from an iron overload and increase of some cytokines, such as interleukin1-beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha). The objective of this study was to study the effect of interaction between ferric ammonium citrate (FAC) and cytokines, IL-1 beta and TNF-alpha, on 1.1B4 human pancreatic beta-cell line.

Methods: The effect of the combination of FAC and cytokines on cell viability was studied by MTT assay. Insulin secretion was assessed by the enzyme-linked immunosorbent assay (ELISA). The reactive oxygen species (ROS) and cell apoptosis in normal and high glucose condition were determined by flow cytometer.

In addition, gene expression of apoptosis, antioxidant; glutathione peroxidase 1 (GPX1) and superoxide dismutase 2 (SOD2), and insulin secretory function were studied by real-time polymerase chain reaction (Real-time PCR).

Results: The findings revealed that FAC exposure resulted in the decrease of cell viability and insulin-release, and the induction of ROS and apoptosis in pancreatic cells. Interestingly, a combination of FAC and cytokines had an additive effect on SOD2 antioxidants' genes expression and endoplasmic reticulum (ER) stress.

In addition, it reduced the insulin secretion genes expression; insulin (INS), glucose kinase (GCK), protein convertase 1 (PSCK1), and protein convertase 2 (PSCK2). Moreover, the highest ROS and the lowest insulin secretion were found in FAC combined with IL-1 beta and TNF-alpha in the high-glucose condition of human pancreatic beta cell, which could be involved in the mechanism of DM development in beta-thalassemia patients