Macrophage migration inhibitory factor deficiency protects pancreatic islets from palmitic acid-induced apoptosis
Само за регистроване кориснике
2012
Аутори
Saksida, TamaraStošić-Grujičić, Stanislava
Timotijević, Gordana
Sandler, Stellan
Stojanović, Ivana
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
As a result of chronic exposure to high levels of free fatty acids, glucose and inflammatory mediators beta-cell apoptosis occurs at the end stage of obesity-associated type 2 diabetes (T2D). One potentially deleterious molecule for beta-cell function associated with T2D and obesity in humans is macrophage migration inhibitory factor (MIF). Therefore, the aim of this study was to explore MIF expression in vivo during development of obesity and insulin resistance in high-fat diet (HFD)-fed C57BL/6 mice and whether MIF inhibition could affect beta-cell apoptosis and dysfunction induced by palmitic acid (PA) in vitro. Indeed, increase in systemic and locally produced MIF correlated well with the weight gain, triglyceride upregulation, glucose intolerance and insulin resistance, which developed in HFD-fed mice. In in vitro settings PA dose-dependently induced MIF secretion before apoptosis development in islets. Further, mif gene deletion, mRNA silencing or protein inhibition rescued beta-...cells from PA-induced apoptosis as measured by MTT assay and histone-DNA enzyme linked immuno sorbent assay. Protection from induced apoptosis was mediated by altered activation of caspase pathway and correlated with changes in the level of Bcl-2 family members. Further, MIF inhibition conveyed a significant resistance to PA-induced downregulation of insulin and PDX-1 expression and ATP content. However, beta-cell function was not entirely preserved in the absence of MIF judging by low glucose oxidation and depolarized mitochondria! membrane. In conclusion, the observed considerable preservation of beta-cells from nutrient-induced apoptosis might implicate MIF as a potential therapeutic target in the later stage of obesity-associated T2D. Immunology and Cell Biology (2012) 90, 688-698; doi:10.1038/icb.2011.89; published online 8 November 2011
Кључне речи:
type 2 diabetes / palmitic acid / obesity / macrophage migration inhibitory factor / beta-cells / apoptosisИзвор:
Immunology and Cell Biology, 2012, 90, 7, 688-698Издавач:
- Wiley, Hoboken
Финансирање / пројекти:
- EASD/AstraZeneca Young Investigator Award
- Молекуларни механизми физиолошке и фармаколошке контроле инфламације и канцера (RS-MESTD-Basic Research (BR or ON)-173013)
DOI: 10.1038/icb.2011.89
ISSN: 0818-9641
PubMed: 22064706
WoS: 000307611700005
Scopus: 2-s2.0-84864859658
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Saksida, Tamara AU - Stošić-Grujičić, Stanislava AU - Timotijević, Gordana AU - Sandler, Stellan AU - Stojanović, Ivana PY - 2012 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/552 AB - As a result of chronic exposure to high levels of free fatty acids, glucose and inflammatory mediators beta-cell apoptosis occurs at the end stage of obesity-associated type 2 diabetes (T2D). One potentially deleterious molecule for beta-cell function associated with T2D and obesity in humans is macrophage migration inhibitory factor (MIF). Therefore, the aim of this study was to explore MIF expression in vivo during development of obesity and insulin resistance in high-fat diet (HFD)-fed C57BL/6 mice and whether MIF inhibition could affect beta-cell apoptosis and dysfunction induced by palmitic acid (PA) in vitro. Indeed, increase in systemic and locally produced MIF correlated well with the weight gain, triglyceride upregulation, glucose intolerance and insulin resistance, which developed in HFD-fed mice. In in vitro settings PA dose-dependently induced MIF secretion before apoptosis development in islets. Further, mif gene deletion, mRNA silencing or protein inhibition rescued beta-cells from PA-induced apoptosis as measured by MTT assay and histone-DNA enzyme linked immuno sorbent assay. Protection from induced apoptosis was mediated by altered activation of caspase pathway and correlated with changes in the level of Bcl-2 family members. Further, MIF inhibition conveyed a significant resistance to PA-induced downregulation of insulin and PDX-1 expression and ATP content. However, beta-cell function was not entirely preserved in the absence of MIF judging by low glucose oxidation and depolarized mitochondria! membrane. In conclusion, the observed considerable preservation of beta-cells from nutrient-induced apoptosis might implicate MIF as a potential therapeutic target in the later stage of obesity-associated T2D. Immunology and Cell Biology (2012) 90, 688-698; doi:10.1038/icb.2011.89; published online 8 November 2011 PB - Wiley, Hoboken T2 - Immunology and Cell Biology T1 - Macrophage migration inhibitory factor deficiency protects pancreatic islets from palmitic acid-induced apoptosis EP - 698 IS - 7 SP - 688 VL - 90 DO - 10.1038/icb.2011.89 ER -
@article{ author = "Saksida, Tamara and Stošić-Grujičić, Stanislava and Timotijević, Gordana and Sandler, Stellan and Stojanović, Ivana", year = "2012", abstract = "As a result of chronic exposure to high levels of free fatty acids, glucose and inflammatory mediators beta-cell apoptosis occurs at the end stage of obesity-associated type 2 diabetes (T2D). One potentially deleterious molecule for beta-cell function associated with T2D and obesity in humans is macrophage migration inhibitory factor (MIF). Therefore, the aim of this study was to explore MIF expression in vivo during development of obesity and insulin resistance in high-fat diet (HFD)-fed C57BL/6 mice and whether MIF inhibition could affect beta-cell apoptosis and dysfunction induced by palmitic acid (PA) in vitro. Indeed, increase in systemic and locally produced MIF correlated well with the weight gain, triglyceride upregulation, glucose intolerance and insulin resistance, which developed in HFD-fed mice. In in vitro settings PA dose-dependently induced MIF secretion before apoptosis development in islets. Further, mif gene deletion, mRNA silencing or protein inhibition rescued beta-cells from PA-induced apoptosis as measured by MTT assay and histone-DNA enzyme linked immuno sorbent assay. Protection from induced apoptosis was mediated by altered activation of caspase pathway and correlated with changes in the level of Bcl-2 family members. Further, MIF inhibition conveyed a significant resistance to PA-induced downregulation of insulin and PDX-1 expression and ATP content. However, beta-cell function was not entirely preserved in the absence of MIF judging by low glucose oxidation and depolarized mitochondria! membrane. In conclusion, the observed considerable preservation of beta-cells from nutrient-induced apoptosis might implicate MIF as a potential therapeutic target in the later stage of obesity-associated T2D. Immunology and Cell Biology (2012) 90, 688-698; doi:10.1038/icb.2011.89; published online 8 November 2011", publisher = "Wiley, Hoboken", journal = "Immunology and Cell Biology", title = "Macrophage migration inhibitory factor deficiency protects pancreatic islets from palmitic acid-induced apoptosis", pages = "698-688", number = "7", volume = "90", doi = "10.1038/icb.2011.89" }
Saksida, T., Stošić-Grujičić, S., Timotijević, G., Sandler, S.,& Stojanović, I.. (2012). Macrophage migration inhibitory factor deficiency protects pancreatic islets from palmitic acid-induced apoptosis. in Immunology and Cell Biology Wiley, Hoboken., 90(7), 688-698. https://doi.org/10.1038/icb.2011.89
Saksida T, Stošić-Grujičić S, Timotijević G, Sandler S, Stojanović I. Macrophage migration inhibitory factor deficiency protects pancreatic islets from palmitic acid-induced apoptosis. in Immunology and Cell Biology. 2012;90(7):688-698. doi:10.1038/icb.2011.89 .
Saksida, Tamara, Stošić-Grujičić, Stanislava, Timotijević, Gordana, Sandler, Stellan, Stojanović, Ivana, "Macrophage migration inhibitory factor deficiency protects pancreatic islets from palmitic acid-induced apoptosis" in Immunology and Cell Biology, 90, no. 7 (2012):688-698, https://doi.org/10.1038/icb.2011.89 . .