Foodborne Cereulide Causes Beta-Cell Dysfunction and Apoptosis

摘要: Aims/Hypothesis To study the effects of cereulide, a food toxin often found at low concentrations in take-away meals, on beta-cell survival and function. Methods Cell death was quantified by Hoechst/Propidium Iodide mouse (MIN6) rat (INS-1E) lines, whole islets control cell lines (HepG2 COS-1). Beta-cell function studied glucose-stimulated insulin secretion (GSIS). Mechanisms toxicity were evaluated MIN6 cells mRNA profiling, electron microscopy mitochondrial tests. Results 24 h exposure to 5 ng/ml cereulide rendered almost all MIN6, INS-1E pancreatic apoptotic, whereas did not increase lines. In murine islets, GSIS capacity lost following 24 0.5 (P<0.05). Cereulide induced markers stress including Puma (p53 up-regulated modulator apoptosis, P<0.05) general pro-apoptotic signals as Chop (CCAAT/-enhancer-binding protein homologous protein). Mitochondria appeared swollen upon transmission microscopy, basal respiration rate reduced 52% (P<0.05) reactive oxygen species increased more than twofold 0.25 0.50 respectively. Conclusions/Interpretation Cereulide causes apoptotic impairs even lower concentrations, with dysfunction underlying these defects. Thus, too cause systemic appears deleterious beta-cell.