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

PeerJ

article

Patchara Rattanaporn¹  Sissades Tongsima³  Thomas Mandrup-Poulsen⁵  Saovaros Svasti²  Dalina Tanyong¹ 

[1] Department of Clinical Microscopic, Faculty of Medical Technology, Mahidol University;Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University;National Biobank of Thailand, National Science and Technology Development Agency;National Center for Genetics Engineering and Biotechnology, National Science and Technology Development Agency;Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen;Department of Biochemistry, Faculty of Science, Mahidol University

关键词: Ferric ammonium citrate;    Cytokines;    Pancreatic beta cell;    Thalassemia;    Diabetes;    Insulin;    Apoptosis;    Reactive oxygen species;    ER stress;    Iron overload;   

DOI  :  10.7717/peerj.9298

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

Background Diabetes 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. 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-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.

【 授权许可】

CC BY