Chronic
Exposure to Tributyltin Chloride Induces Pancreatic
Islet Cell Apoptosis and Disrupts Glucose Homeostasis in Male Mice
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Abstract
It has been reported
that organotin compounds such as triphenyltin
or tributyltin (TBT) induce diabetes and insulin resistance. However,
histopathological effects of organotin compounds on the Islets of
Langerhans and exocrine pancreas are still unclear. In the present
study, male KM mice were orally administered with TBT (0.5, 5, and
50 μg/kg) once every 3 days. The fasting plasma glucose levels
significantly elevated, and the levels of serum insulin or glucagon
decreased in the animals treated with TBT for 60 days. In animals
treated for 45 days, the number of apoptotic cells in the islets and
exocrine pancreas was elevated in a dose-dependent manner. The percentage
of proliferating (PCNA-positive) cells was decreased in the islets,
while it was increased in exocrine acinar cells. Immunohistochemistry
analysis showed that estrogen receptor (ER) and androgen receptor
(AR) were present in vascular endothelium, ductal cells, and islet
cells, but absent from pancreatic exocrine cells. TBT exposure decreased
the production of estradiol and triiodothyronine and elevated the
concentration of testosterone, and resulted in a decrease of ERα
expression and an elevation of AR in the pancreas measured by Western
boltting. The results suggested that TBT inhibited the proliferation
and induced the apoptosis of islet cells via multipathways, causing
a decrease of relative islet area in the animals treated for 60 days,
which could result in a disruption of glucose homeostasis. The different
presence of ERs and AR between the islets and exocrine pancreas might
be one of reasons causing different effects on cell proliferation