All-trans Retinoic acid (atRA) is instructive for the development of
endocrine pancreas and is an integral component of b-cell induction protocols.
We showed that atRA induces glucose-responsive endocrine transdifferentiation
of pleomorphic pancreatic ductal adenocarcinoma cells in
vitro. This study aimed to detect the role of atRA in improving the histological
changes of the pancreas in diabetic rats. Forty young male Wistar
rats were used and divided into three groups. Group I: normal vehicle
control (N55). Group II: streptozotocin-induced diabetic rats (N520)
were followed up at 0.0, 1, 2, and 4 weeks. Group III: streptozotocininduced
diabetic rats (N515) treated with atRA (2.5 mg/kg/day), were
followed up at 1, 2, and 4 weeks. Specimens from the pancreas were processed
for light, electron microscopy and pancreatic insulin mRNA expression.
Blood samples were assayed for the levels of glucose, insulin, and
total peroxides. In the atRA-treated group, the number of the islets and
the islet area significantly increased. Strong insulin-immunoreactive
endocrine-like cells were observed nearby the pancreatic acini and the
interlobular ducts. Interestingly, insulin-positive cells seemed to arise
from pancreatic acinar and ductal epithelium. Ultrastructurally, ß-cells,
acinar, and ductal cells restored their normal appearance. Pancreatic
insulin mRNA and blood indices were almost normalized. AtRA improved
the histological changes of the pancreas and the blood indices in diabetic
rats.