-
Combination of ferric ammonium citrate with cytokines involved in apoptosis and insulin secretion of human pancreatic beta cells related to diabetes in thalassemia
- Back
Document Title
Combination of ferric ammonium citrate with cytokines involved in apoptosis and insulin secretion of human pancreatic beta cells related to diabetes in thalassemia
Author
Rattanaporn P., Tongsima S., Mandrup-Poulsen T., Svasti S., Tanyong D.
Name from Authors Collection
Affiliations
Department of Clinical Microscopic, Faculty of Medical Technology, Mahidol University, Nakhon Pathom, Thailand; Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand; National Biobank of Thailand, National Science and Technology Development Agency, Pathum Thani, Thailand; National Center for Genetics Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani, Thailand; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand
Type
Article
Source Title
PeerJ
ISSN
21678359
Year
2020
Volume
2020
Issue
6
Open Access
Gold, Green
Publisher
PeerJ Inc.
DOI
10.7717/peerj.9298
Abstract
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-a (TNF-a). The objective of this study was to study the effect of interaction between ferric ammonium citrate (FAC) and cytokines, IL-1β and TNF-a, 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-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. © 2020 Rattanaporn et al.
Keyword
Apoptosis | Cytokines | Diabetes | ER stress | Ferric ammonium citrate | insulin | Iron overload | Pancreatic beta cell | Reactive oxygen species
Industrial Classification
Knowledge Taxonomy Level 1
Knowledge Taxonomy Level 2
Knowledge Taxonomy Level 3
Funding Sponsor
Office of the Higher Education Commission; Mahidol University; National Science and Technology Development Agency; Thailand Graduate Institute of Science and Technology
License
CC BY
Rights
Author
Publication Source
Scopus