2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces calcium influx through T-type calcium channel and enhances lysosomal exocytosis and insulin secretion in INS-1 cells

Youn Hee Kim, Young Jun Shim, Yong Jae Shin, Donggeun Sul, Eunil Lee, Bon Hong Min

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has been associated with diabetes in several epidemiological studies. However, the diabetogenic action of TCDD on pancreatic cells is unclear. Here, we investigated the direct toxic effects of TCDD on a rat insulin-secreting beta cell line. We found that TCDD enhances exocytosis of MTT formazan and lysosomal proteins such as β-hexosaminindase and Lamp-1. This TCDD-induced exocytosis was abrogated by T-type calcium channel blockers (mibefradil, flunarizine) but not by an aryl hydrocarbon receptor antagonist (α-naphtoflavone). Indeed, cytosolic calcium levels were increased by TCDD. Furthermore, TCDD stimulated insulin secretion, which was inhibited by flunarizine. Taken together, our results suggest that TCDD-induced calcium influx via T-type channels regulates vesicular trafficking, such as lysosomal and secretory granule exocytosis, and that TCDD might exert adverse effects on beta cells by continuous insulin release followed by beta cell exhaustion. This could contribute to the link between TCDD exposure and the risk of developing diabetes.

Original languageEnglish
Pages (from-to)151-161
Number of pages11
JournalInternational Journal of Toxicology
Volume28
Issue number3
DOIs
Publication statusPublished - 2009

Keywords

  • Exocytosis
  • Insulin
  • Lysosomes
  • T-type calcium channel
  • TCDD

ASJC Scopus subject areas

  • Toxicology

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