Transcriptional regulation of cyclooxygenase-2 gene in pancreatic beta-
cells.
Prostaglandin E(2) (PGE(2)) has been shown to negatively affect
pancreatic beta-cell function, and its inducible synthesis is mediated
in part by cycloxygenase-2 (COX-2)...COX-2 promoter activity was also
increased by 2,3,7,8-tetrachlorodibenzo-p-dioxin, an AhR
activator, ... 2,3,7,8-tetrachlorodibenzo-p-dioxin increased COX-2
mRNA in a dose-dependent manner... PMID: 15213229

The stimulation of tumor necrosis factor and inhibition of glucose
transport and lipoprotein lipase in adipose cells by 2,3,7,8-
tetrachlorodibenzo-p-dioxin.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is found throughout the
environment in industrialized countries, and most people have had some
exposure. TCDD has very high lipid solubility and is concentrated in
adipose tissue. Because an epidemiologic association between TCDD
exposure and diabetes has been described, we examined the effects of
TCDD in adipocytes. The addition of TCDD to 3T3-F442a cells, both at
the initiation of differentiation and after cells were fully
differentiated, resulted in a 2-fold increase in the secretion of
tumor necrosis factor (TNF). When added during differentiation, there
was also a 25% decrease in lipid accumulation. In addition to the
stimulation of TNF, TCDD affected glucose transport and lipoprotein
lipase (LPL) activity. When added to cultures of cells that were
undergoing differentiation, TCDD inhibited total 2-deoxyglucose
transport in a dose-dependent fashion, with 50% inhibition of glucose
transport when added to cultures for 48 hours at 5 nmol/L TCDD. In
addition, when cells were exposed to 50 nmol/L TCDD for 48 hours,
there was a 40% reduction in LPL activity. Thus, the addition of TCDD
to adipocyte cultures resulted in an increase in TNF secretion and a
decrease in glucose transport and LPL activity. Because TCDD is
concentrated in adipose tissue, these studies provide a possible
physiologic mechanism for epidemiologic studies that link dioxin to
diabetes. PMID: 11782874

Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is associated
with hyperinsulinemia and insulin resistance.
High exposures of Vietnam veterans to 2,3,7, 8-Tetrachlorodibenzo-p-
dioxin, a dioxin contained in the herbicide mixture Agent Orange, have
previously been demonstrated to be associated with an increased
prevalence of diabetes and hyperinsulinemia in non-diabetic subjects.
Sixty-nine persons were identified who were in good health and had
normal glucose levels during glucose tolerance testing. These subjects
lived within 25 miles of the Vertac/Hercules Superfund site located in
Jacksonville, Arkansas. The blood sera lipid concentrations of TCDD
for the 69 subjects ranged between 2 and 94 ppt. When subjects with
blood sera lipid TCDD levels in the top 10% (TCDD > 15 ppt, n = 7)
were compared to subjects with lower levels (2-15 ppt, n = 62), there
were no group differences in age, obesity, gender distribution, total
lipids, or glucose levels. However, plasma insulin concentrations, at
fasting and 30, 60, and 120 min following a 75 g glucose load, were
significantly higher in the group with high blood TCDD levels. These
finding could not be explained by other known risk factors for
hyperinsulinemia. The finding of the TCDD-hyperinsulinemia
relationship is consistent with studies of Vietnam veterans and
suggests that high blood TCDD levels may cause insulin resistance.
PMID: 10911003

Evaluation of diabetes mellitus, serum glucose, and thyroid function
among United States workers exposed to 2,3,7,8-tetrachlorodibenzo-p-
dioxin.
OBJECTIVE: Some studies suggest that exposure to 2,3,7,8-
tetrachlorodibenzo-p-dioxin (TCDD) may affect glucose metabolism and
thyroid function. To further assess the relation between exposure to
TCDD and endocrine function, data from the largest morbidity study of
industrial workers exposed to TCDD were examined.... CONCLUSIONS:
These findings provide modest evidence that exposure to TCDD may
affect thyroid function and glucose metabolism.
PMID: 10450245