title: Macrophage migration inhibitory factor (MIF) enhances palmitic acid- and glucose-induced murine beta cell dysfunction and destruction in vitro.
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.
authors.affiliation: Department of Immunology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Serbia. branicevo@yahoo.com
authors.forename: Ivana
authors.initials: I
authors.lastname: Stojanovic
authors.forename: Tamara
authors.initials: T
authors.lastname: Saksida
authors.forename: Gordana
authors.initials: G
authors.lastname: Timotijevic
authors.forename: Stellan
authors.initials: S
authors.lastname: Sandler
authors.forename: Stanislava
authors.initials: S
authors.lastname: Stosic-Grujicic
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D053938:DNA Fragmentation; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D020869:Gene Expression Profiling; D005947:Glucose / Q000378:metabolism*; D066298:In Vitro Techniques; D050417:Insulin-Secreting Cells / Q000166:cytology*; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019308:Palmitic Acid / Q000378:metabolism*; D013778:Tetrazolium Salts / Q000737:chemistry; D013844:Thiazoles / Q000737:chemistry
chemical_list: D016207:Cytokines; D008263:Macrophage Migration-Inhibitory Factors; D013778:Tetrazolium Salts; D013844:Thiazoles; D019308:Palmitic Acid; D053148:Caspase 3; C022616:thiazolyl blue; D005947:Glucose