TY  - JOUR
AU  - Stojanović, Ivana D.
AU  - Saksida, Tamara
AU  - Timotijević, Gordana S
AU  - Sandler, Stellan
AU  - Stošić-Grujičić, Stanislava
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1078
AB  - Although several reports suggest a potentially deleterious role of macrophage migration inhibitory factor (MIF) in type 2 diabetes (T2D) pathology, it is still unclear how this pro-inflammatory cytokine acts on pancreatic beta cells. The aim of the present study was to evaluate MIF effects on murine beta cells in the in vitro settings mimicking T2D-associated conditions. Results indicate that recombinant MIF further increased apoptosis of pancreatic islets or MIN6 cells upon exposure to palmitic acid or glucose. This was accompanied by upregulation of several pro-apoptotic molecules. Furthermore, MIF potentiated nutrient-induced islet cell dysfunction, as revealed by lower glucose oxidation rate, ATP content, and depolarized mitochondrial membrane. The final outcome was potentiation of mitochondrial apoptotic pathway. The observed upregulation of nutrient-induced islet cell dysfunction and apoptosis by MIF implicates that silencing MIF may be beneficial for maintaining integrity of endocrine pancreas in obesity-associated T2D.
T2  - Growth Factors
T1  - Macrophage migration inhibitory factor (MIF) enhances palmitic acid-and glucose-induced murine beta cell dysfunction and destruction in vitro
IS  - 6
VL  - 30
SP  - 111
EP  - 393
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1078
ER  - 

@article{
author = "Stojanović, Ivana D. and Saksida, Tamara and Timotijević, Gordana S and Sandler, Stellan and Stošić-Grujičić, Stanislava",
year = "2012",
abstract = "Although several reports suggest a potentially deleterious role of macrophage migration inhibitory factor (MIF) in type 2 diabetes (T2D) pathology, it is still unclear how this pro-inflammatory cytokine acts on pancreatic beta cells. The aim of the present study was to evaluate MIF effects on murine beta cells in the in vitro settings mimicking T2D-associated conditions. Results indicate that recombinant MIF further increased apoptosis of pancreatic islets or MIN6 cells upon exposure to palmitic acid or glucose. This was accompanied by upregulation of several pro-apoptotic molecules. Furthermore, MIF potentiated nutrient-induced islet cell dysfunction, as revealed by lower glucose oxidation rate, ATP content, and depolarized mitochondrial membrane. The final outcome was potentiation of mitochondrial apoptotic pathway. The observed upregulation of nutrient-induced islet cell dysfunction and apoptosis by MIF implicates that silencing MIF may be beneficial for maintaining integrity of endocrine pancreas in obesity-associated T2D.",
journal = "Growth Factors",
title = "Macrophage migration inhibitory factor (MIF) enhances palmitic acid-and glucose-induced murine beta cell dysfunction and destruction in vitro",
number = "6",
volume = "30",
pages = "111-393",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1078"
}

Stojanović, I. D., Saksida, T., Timotijević, G. S., Sandler, S.,& Stošić-Grujičić, S.. (2012). Macrophage migration inhibitory factor (MIF) enhances palmitic acid-and glucose-induced murine beta cell dysfunction and destruction in vitro. in Growth Factors, 30(6), 111-393.
https://hdl.handle.net/21.15107/rcub_ibiss_1078

Stojanović ID, Saksida T, Timotijević GS, Sandler S, Stošić-Grujičić S. Macrophage migration inhibitory factor (MIF) enhances palmitic acid-and glucose-induced murine beta cell dysfunction and destruction in vitro. in Growth Factors. 2012;30(6):111-393.
https://hdl.handle.net/21.15107/rcub_ibiss_1078 .

Stojanović, Ivana D., Saksida, Tamara, Timotijević, Gordana S, Sandler, Stellan, Stošić-Grujičić, Stanislava, "Macrophage migration inhibitory factor (MIF) enhances palmitic acid-and glucose-induced murine beta cell dysfunction and destruction in vitro" in Growth Factors, 30, no. 6 (2012):111-393,
https://hdl.handle.net/21.15107/rcub_ibiss_1078 .

TY  - JOUR
AU  - Saksida, Tamara
AU  - Stošić-Grujičić, Stanislava
AU  - Timotijević, Gordana S
AU  - Sandler, Stellan
AU  - Stojanović, Ivana D.
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1154
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
T2  - Immunology and Cell Biology
T1  - Macrophage migration inhibitory factor deficiency protects pancreatic islets from palmitic acid-induced apoptosis
IS  - 7
VL  - 90
SP  - 619
EP  - 698
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1154
ER  - 

@article{
author = "Saksida, Tamara and Stošić-Grujičić, Stanislava and Timotijević, Gordana S and Sandler, Stellan and Stojanović, Ivana D.",
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",
journal = "Immunology and Cell Biology",
title = "Macrophage migration inhibitory factor deficiency protects pancreatic islets from palmitic acid-induced apoptosis",
number = "7",
volume = "90",
pages = "619-698",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1154"
}

Saksida, T., Stošić-Grujičić, S., Timotijević, G. S., Sandler, S.,& Stojanović, I. D.. (2012). Macrophage migration inhibitory factor deficiency protects pancreatic islets from palmitic acid-induced apoptosis. in Immunology and Cell Biology, 90(7), 619-698.
https://hdl.handle.net/21.15107/rcub_ibiss_1154

Saksida T, Stošić-Grujičić S, Timotijević GS, Sandler S, Stojanović ID. Macrophage migration inhibitory factor deficiency protects pancreatic islets from palmitic acid-induced apoptosis. in Immunology and Cell Biology. 2012;90(7):619-698.
https://hdl.handle.net/21.15107/rcub_ibiss_1154 .

Saksida, Tamara, Stošić-Grujičić, Stanislava, Timotijević, Gordana S, Sandler, Stellan, Stojanović, Ivana D., "Macrophage migration inhibitory factor deficiency protects pancreatic islets from palmitic acid-induced apoptosis" in Immunology and Cell Biology, 90, no. 7 (2012):619-698,
https://hdl.handle.net/21.15107/rcub_ibiss_1154 .