Inhibition of phosphoenolpyruvate carboxykinase activity appears to be the key biochemical lesion in the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in rats

Weber, Lutz W. D.; Stahl, Bernhard; Lebofsky, Margitta; Alper, Richard H.; Kerecsen, Laszlo; Rozman, Karl K.

doi:10.1016/0045-6535(91)90044-e

Cited by 14 publications

(6 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hence, reduced basal corticosterone production may result in insufficient induction of key intermediary metabolic enzymes. Although the long-term consequences of down regulation of intermediary metabolic enzymes were not investigated in the present study, it is possible that deficits in gluconeogenic or lipogenic activity may play roles in the wasting observed in young chicks in highly contaminated areas within the Great Lakes basin (13,59 (61)(62)(63).…”

Section: Discussionmentioning

confidence: 95%

Relationships between environmental organochlorine contaminant residues, plasma corticosterone concentrations, and intermediary metabolic enzyme activities in Great Lakes herring gull embryos.

Lorenzen¹,

Moon²,

Kennedy³

et al. 1999

Environ Health Perspect

View full text Add to dashboard Cite

Expeniments were conducted to survey and detect diferences in plasma corticosterone concentrations and intermediary metabolic enzyme activities in herring gull (Lawus aynta) embryos environmentally exposed to organohlorne contamants n ovo. Unincubated fertile herring l e were colecd from an Atlantic coast contol site and various GreatLakes sites in 1997 and arifilly inuat in laborator. Liver and/or kidney tiues fom approxately h of the late-stage embryos were analyzed for the a es of various intermediary metabolic enzymes known to be regulated, at leat in part, by corticoternids. Bal plsma coticosterone concentrations were determined for the remaining embryos.

show abstract

Section: Discussionmentioning

confidence: 95%

Relationships between environmental organochlorine contaminant residues, plasma corticosterone concentrations, and intermediary metabolic enzyme activities in Great Lakes herring gull embryos.

Lorenzen¹,

Moon²,

Kennedy³

et al. 1999

Environ Health Perspect

View full text Add to dashboard Cite

show abstract

“…These epidemiological observations are supported by several experimental studies. Exposure to TCDD was found to aff ect glucose metabolism such as a decrease in glucose uptake by the pancreas and adipose tissue in the guinea pig (Enan et al, 1992) and an alteration of gluconeogenesis and PEPCK activity in the rat (Weber et al, 1991). Other studies also reported the eff ects of TCDD on glucose metabolism, including impairment of insulin secretion in rats (Novelli et al, 2005) and glucose tolerance in mice (Ishida et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

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

Kurita

Yoshioka

Nishimura

et al. 2009

J of Applied Toxicology

View full text Add to dashboard Cite

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.

show abstract

“…It has been reported that TCDD dose dependently inhibits PEPCK in healthy rats within 8 days. A dose of 15 μg/kg TCDD reduced respective enzyme activity by approximately 35% (Weber et al, 1991c). The same dose caused stagnation of body weight in NDB rats for 1 week and very slow weight gain thereafter .…”

Section: Discussionmentioning

confidence: 94%

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) reverses hyperglycemia in a type II diabetes mellitus rat model by a mechanism unrelated to PPARγ

Fried

Guo

Esterly

et al. 2010

Drug and Chemical Toxicology

View full text Add to dashboard Cite

It has been asserted that exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increases the risk for diabetes mellitus in humans, observable as hyperglycemia resulting from insulin resistance. There is no animal model for the induction of diabetes by TCDD. On the contrary, TCDD has been shown to increase insulin sensitivity in rats. Therefore, a diabetic rat model was used to study the effects of TCDD on preexisting diabetes. Type II diabetes was induced in male rats by a high-fat diet and streptozotocin. After manifestation of the disease, these rats received loading dose rates (LDRs) of 3.2, 6.4, and 12.8 microg/kg of TCDD p.o., followed by weekly maintenance dose rates. Rats fed a high-fat diet and not dosed with streptozotocin nor with TCDD served as nondiabetic controls. By day 2, serum-glucose levels in diabetic rats treated with the high LDR of 12.8 microg/kg TCDD were already significantly reduced. By day 8, serum-glucose levels had decreased to control levels and were maintained for the duration of the study (32 days). Thus, TCDD effectively counteracted hyperglycemia in this diabetic rat model. In healthy animals, TCDD induced PPAR gamma transcription and activity in a different dose range than that observed for the hypoglycemic effect.

show abstract

Inhibition of phosphoenolpyruvate carboxykinase activity appears to be the key biochemical lesion in the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in rats

Cited by 14 publications

References 21 publications

Relationships between environmental organochlorine contaminant residues, plasma corticosterone concentrations, and intermediary metabolic enzyme activities in Great Lakes herring gull embryos.

Relationships between environmental organochlorine contaminant residues, plasma corticosterone concentrations, and intermediary metabolic enzyme activities in Great Lakes herring gull embryos.

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

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) reverses hyperglycemia in a type II diabetes mellitus rat model by a mechanism unrelated to PPARγ

Contact Info

Product

Resources

About