Abstract
BackgroundDiabetes mellitus (DM) is a common complication found in β-thalassemia patients. The mechanism of DM in β-thalassemia patients is still unclear, but it could be from an iron overload and increase of some cytokines, such as interleukin1-β (IL-1β) and tumor necrosis factor-α (TNF-α). The objective of this study was to study the effect of interaction between ferric ammonium citrate (FAC) and cytokines, IL-1β and TNF-α, on 1.1B4 human pancreatic β-cell line.MethodsThe 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).ResultsThe 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-1β and TNF-α in the high-glucose condition of human pancreatic beta cell, which could be involved in the mechanism of DM development in β-thalassemia patients.
Highlights
One of the hereditary blood disorders resulting from a defect in β-globin chain synthesis is β-thalassemia, which is caused by point mutation or, more rarely, deletion of the β-globin gene (Galanello & Origa, 2010)
ferric ammonium citrate (FAC) induce reactive oxygen species (ROS) production, reduce cell viability, and decrease insulin expression of pancreatic β-cell The accumulated iron in β-cell islets might promote ROS levels and cell apoptosis leading to a decrease in insulin production
Expression of apoptotic regulatory proteins include BAX, B-cell lymphoma 2 (BCL2) and signal transducer and activator of transcription 1 (STAT1) were assessed to study the effect of FAC on β-cell apoptosis
Summary
One of the hereditary blood disorders resulting from a defect in β-globin chain synthesis is β-thalassemia, which is caused by point mutation or, more rarely, deletion of the β-globin gene (Galanello & Origa, 2010). Several mechanisms involved in DM development in β-thalassemia patients were reported including insulin resistance, hepatic dysfunction, and insulin deficiency resulting from β-cell damage or apoptosis (Noetzli et al, 2012; Ghergherehchi & Habibzadeh, 2015; Li et al, 2014). A combination of FAC and cytokines had an additive effect on SOD2 antioxidants’ genes expression and endoplasmic reticulum (ER) stress It reduced the insulin secretion genes expression; insulin (INS), glucose kinase (GCK), protein convertase 1 (PSCK1), and protein convertase 2 (PSCK2). The highest ROS and the lowest insulin secretion were found in FAC combined with IL-1β and TNF-a in the high-glucose condition of human pancreatic beta cell, which could be involved in the mechanism of DM development in β-thalassemia patients
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