title: 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.
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 mug/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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Ishida
authors.forename: Shoko
authors.initials: S
authors.lastname: Kan-o
authors.forename: Junpei
authors.initials: J
authors.lastname: Mutoh
authors.forename: Shuso
authors.initials: S
authors.lastname: Takeda
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ishii
authors.forename: Isamu
authors.initials: I
authors.lastname: Hashiguchi
authors.forename: Akifumi
authors.initials: A
authors.lastname: Akamine
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yamada
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D004187:Disaccharides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004386:Duodenum / Q000187:drug effects* / Q000473:pathology*; D004847:Epithelial Cells / Q000187:drug effects / Q000648:ultrastructure; D005951:Glucose Tolerance Test; D006041:Goats; D007441:Intubation, Gastrointestinal; D008297:Male; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008871:Microvilli / Q000187:drug effects / Q000648:ultrastructure; D009004:Monosaccharide Transport Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage / Q000009:adverse effects*; D012333:RNA, Messenger; D011817:Rabbits; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects* / Q000378:metabolism; D051269:Sodium-Glucose Transporter 1; D013045:Species Specificity; D013393:Sucrase / Q000096:biosynthesis / Q000187:drug effects; D000520:alpha-Glucosidases / Q000096:biosynthesis / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D004187:Disaccharides; D008562:Membrane Glycoproteins; D009004:Monosaccharide Transport Proteins; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; C495675:Slc5a1 protein, mouse; D051269:Sodium-Glucose Transporter 1; D000520:alpha-Glucosidases; D013393:Sucrase