Aryl hydrocarbon receptor‐mediated effects of 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin on glucose‐stimulated insulin secretion in mice

Abstract

Epidemiological and laboratory studies suggested that exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) affects glucose homeostasis and increases the incidence of type 2 diabetes mellitus. To evaluate the effects of TCDD on insulin secretion from islets of Langerhans (islets), we designed in vivo, ex vivo and in vitro experiments. For the in vivo experiment, male C57BL/6J and aryl hydrocarbon receptor (AhR)-null mice were injected intraperitoneally with TCDD (10 microg kg(-1) b.w.), fasted for 12 h and administered glucose 24 h post-administration. TCDD exposure significantly decreased the plasma insulin concentration at 60 and 120 min after a glucose challenge in C57BL/6J mice but not in AhR-null mice. In contrast, the plasma glucose concentration was not changed by TCDD exposure in both C57BL/6J and AhR-null mice. For the ex vivo experiment, we isolated islets 24 h after TCDD administration and determined the glucose-stimulated insulin secretion from the islets. The insulin secretion level was found to be significantly decreased by TCDD exposure at 60 min after glucose treatment. For the in vitro experiment, islets harvested from untreated C57BL/6J mice were exposed to 0.1, 1, 10 or 100 nM TCDD for 24 h and analyzed for glucose-stimulated insulin secretion. Insulin secretion from the islets remained unchanged regardless of TCDD dose. In conclusion, TCDD exposure impaired the second phase of glucose-stimulated secretion of insulin from the islets via the AhR signaling pathway.

Influence of dioxin on the daily variation of insulin sensitivity in mice

“…In this study, TCDD treatment decreased the insulin sensitivity, and subsequently elevated plasma insulin concentration at ZT16. Kurita et al (2009) reported that TCDD (10,000 ng/kg, intraperitoneal) decreased plasma insulin concentration in mice, which is different from the present finding. Tolerable Daily Intake (TDI) of dioxin is estimated to be 100 ng/kg in mice (Ministry of Health, Labour and Welfare of Japan, 1999).…”

Chronic Exposure to Aroclor 1254 Disrupts Glucose Homeostasis in Male Mice via Inhibition of the Insulin Receptor Signal Pathway

“…16 Treatment with TCDD (100 μg/kg per day) for 10 days alters glucose tolerance, 17 but a single dose of 10 μg/kg decreases only plasma insulin levels. 18 TCDD at a dose as low as 0.03 μg/kg (single intraperitoneal) causes a significant reduction in the glucose transporting activity of guinea pig adipose tissue and pancreas. 19 The exposure of adult mice to BPA disrupts pancreatic β-cell function in vivo and induces insulin resistance.…”

Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on adipogenic differentiation and insulin-induced glucose uptake in 3T3-L1 cells

“…Animal studies also have revealed that TCDD exposure inhibits insulin-induced glucose uptake [38] as well as impairs the second phase of glucosestimulated secretion of insulin from islets [39] in mice via the AhR-dependent signals. Previous in vitro studies showed that TCDD significantly reduced the basal [40] as well as the insulininduced glucose uptake [41] by differentiated 3T3-L1 adipocytes.…”