2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced change in intestinal function and pathology: Evidence for the involvement of arylhydrocarbon receptor-mediated alteration of glucose transportation

Takumi Ishida, Shoko Kan-O, Junpei Mutoh, Shuso Takeda, Yuji Ishii, Isamu Hashiguchi, Akifumi Akamine, Hideyuki Yamada

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Although numerous studies have been performed to clarify the mechanism(s) underlying the toxicological responses induced by dioxins, their effect on the intestine is less well understood. To address this issue, we examined the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the pathology and function of the intestine in arylhydrocarbon receptor (AhR)-sensitive (C57BL/6J) and -less-sensitive (DBA/2J) mice. A single oral administration of TCDD (100 μg/kg) to C57BL/6J mice produced changes in villous structure and nuclear/cytoplasm ratio in the epithelial cells of the intestine. Furthermore, in an oral glucose tolerance test, the serum glucose level was significantly increased in the C57BL/6J mouse but not in the DBA/2J mouse by TCDD treatment. In agreement with this, the expression of intestinal mRNAs coding sodium-glucose co-transporter 1 (SGLT1) and glucose transporter type 2 were increased only in C57BL/6J mice by TCDD. The increase in the former transporter was also confirmed from its protein level. The glucose level in the intestinal contents is thought to be one of the factors contributing to SGLT1 induction. Concerning with this, the intestinal activity of sucrase and lactase was significantly increased only in C57BL/6J mice by TCDD. These results suggest that while TCDD produces initial damage to the intestinal epithelium, the tissues induce SGLT1 to facilitate the absorption of glucose, which is expected, at least partially, to combat the wasting syndrome induced by TCDD. The data provided here also suggest that AhR is involved in the mechanism of SGLT1 induction.

Original languageEnglish
Pages (from-to)89-97
Number of pages9
JournalToxicology and Applied Pharmacology
Volume205
Issue number1
DOIs
Publication statusPublished - May 15 2005

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Pharmacology

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