Combination of ferric ammonium citrate with cytokines involved in apoptosis and insulin secretion of human pancreatic beta cells related to diabetes in thalassemia.

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From: PeerJ(Vol. 8)
Publisher: PeerJ. Ltd.
Document Type: Article
Length: 5,417 words
Lexile Measure: 1370L

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Abstract :

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.

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Gale Document Number: GALE|A626750221