Cell death and impairment of glucose-stimulated insulin secretion induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the β-cell line INS-1E

Simona Piaggi, Michela Novelli, Luisa Martino, Matilde Masini, Chiara Raggi, Enrico Orciuolo, Pellegrino Masiello, Alessandro Casini, Vincenzo De Tata

Research output: Contribution to journalArticle

Abstract

The aim of this research was to characterize 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity on the insulin-secreting β-cell line INS-1E. A sharp decline of cell survival (below 20%) was observed after 1 h exposure to TCDD concentrations between 12.5 and 25 nM. Ultrastructurally, β-cell death was characterized by extensive degranulation, appearance of autophagic vacuoles, and peripheral nuclear condensation. Cytotoxic concentrations of TCDD rapidly induced a dose-dependent increase in intracellular calcium concentration. Blocking calcium entry by EGTA significantly decreased TCDD cytotoxicity. TCDD was also able to rapidly induce mitochondrial depolarization. Interestingly, 1 h exposition of INS-1E cells to very low TCDD concentrations (0.05-1 nM) dramatically impaired glucose-stimulated but not KCl-stimulated insulin secretion. In conclusion, our results clearly show that TCDD exerts a direct β-cell cytotoxic effect at concentrations of 15-25 nM, but also markedly impairs glucose-stimulated insulin secretion at concentrations 20 times lower than these. On the basis of this latter observation we suggest that pancreatic β-cells could be considered a specific and sensitive target for dioxin toxicity.

Original languageEnglish
Pages (from-to)333-340
Number of pages8
JournalToxicology and Applied Pharmacology
Volume220
Issue number3
DOIs
Publication statusPublished - May 1 2007

Keywords

  • Diabetes
  • Dioxin
  • INS-1 cells
  • Insulin secretion

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

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