title: Foodborne cereulide causes beta-cell dysfunction and apoptosis.
abstract: OBJECTIVE
  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 in mouse (MIN6) and rat (INS-1E) beta-cell lines, whole mouse islets and control cell lines (HepG2 and COS-1). Beta-cell function was studied by glucose-stimulated insulin secretion (GSIS). Mechanisms of toxicity were evaluated in MIN6 cells by mRNA profiling, electron microscopy and mitochondrial function tests.
  
  
  RESULTS
  24 h exposure to 5 ng/ml cereulide rendered almost all MIN6, INS-1E and pancreatic islets apoptotic, whereas cell death did not increase in the control cell lines. In MIN6 cells and murine islets, GSIS capacity was lost following 24 h exposure to 0.5 ng/ml cereulide (P<0.05). Cereulide exposure induced markers of mitochondrial stress including Puma (p53 up-regulated modulator of apoptosis, P<0.05) and general pro-apoptotic signals as Chop (CCAAT/-enhancer-binding protein homologous protein). Mitochondria appeared swollen upon transmission electron microscopy, basal respiration rate was reduced by 52% (P<0.05) and reactive oxygen species increased by more than twofold (P<0.05) following 24 h exposure to 0.25 and 0.50 ng/ml cereulide, respectively.
  
  
  CONCLUSIONS
  Cereulide causes apoptotic beta-cell death at low concentrations and impairs beta-cell function at even lower concentrations, with mitochondrial dysfunction underlying these defects. Thus, exposure to cereulide even at concentrations too low to cause systemic effects appears deleterious to the beta-cell.
authors.affiliation: Laboratory for Clinical and Experimental Medicine and Endocrinology, KU Leuven, Leuven, Belgium.
authors.forename: Roman
authors.initials: R
authors.lastname: Vangoitsenhoven
authors.affiliation: Laboratory for Clinical and Experimental Medicine and Endocrinology, KU Leuven, Leuven, Belgium.
authors.forename: Dieter
authors.initials: D
authors.lastname: Rondas
authors.affiliation: Laboratory for Clinical and Experimental Medicine and Endocrinology, KU Leuven, Leuven, Belgium.
authors.forename: Inne
authors.initials: I
authors.lastname: Crèvecoeur
authors.affiliation: Laboratory for Clinical and Experimental Medicine and Endocrinology, KU Leuven, Leuven, Belgium.
authors.forename: Wannes
authors.initials: W
authors.lastname: D'Hertog
authors.affiliation: EM Facility, VIB Bio Imaging Core and VIB department for the Biology of Disease, KU Leuven, Leuven, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Baatsen
authors.affiliation: Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, Pisa, Italy.
authors.forename: Matilde
authors.initials: M
authors.lastname: Masini
authors.affiliation: Food, Medicines, and Consumer Safety, Scientific Institute of Public Health, Brussels, Belgium.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Andjelkovic
authors.affiliation: Food, Medicines, and Consumer Safety, Scientific Institute of Public Health, Brussels, Belgium.
authors.forename: Joris
authors.initials: J
authors.lastname: Van Loco
authors.affiliation: Laboratory for Clinical and Experimental Medicine and Endocrinology, KU Leuven, Leuven, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Matthys
authors.affiliation: Laboratory for Clinical and Experimental Medicine and Endocrinology, KU Leuven, Leuven, Belgium.
authors.forename: Chantal
authors.initials: C
authors.lastname: Mathieu
authors.affiliation: Laboratory for Clinical and Experimental Medicine and Endocrinology, KU Leuven, Leuven, Belgium.
authors.forename: Lut
authors.initials: L
authors.lastname: Overbergh
authors.affiliation: Laboratory for Clinical and Experimental Medicine and Endocrinology, KU Leuven, Leuven, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Van der Schueren
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D047630:Depsipeptides / Q000633:toxicity*; D005516:Food Microbiology; D005947:Glucose / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D051381:Rats
chemical_list: D047630:Depsipeptides; D007328:Insulin; C089294:cereulide; D005947:Glucose