Cytokine-induced expression of inducible nitric oxide synthetase (iNOS) and
production of nitric oxide (NO) by pancreatic islet cells has been suggest
ed as one potential mechanism for beta cell destruction. In this study, we
investigated the role of iNOS and NO in islet primary non-function. Islets
were assessed for their function, viability and expression of iNOS. Adult r
at and pig islets isolated by collagenase digestion and fetal pig pancreas
(FPP) grafts isolated by collagenase digestion or high oxygen culture were
transplanted into C57BL6 mice and nude mice. iNOS protein was detected by i
mmunohistochemistry. iNOS protein was found in normal rat and pig pancreas
and adult rat and pig islets that were isolated by collagenase digestion an
d transplanted into either C57BL6 mice or nude mice. iNOS was not detected
in fetal pig islet grafts, regardless of whether collagenase was used in th
e isolation process. In adult pig islet grafts, the presence of iNOS protei
n correlated with high levels of islet cell apoptosis and primary non-funct
ion. Despite the persistent presence of iNOS in rat islets, there was no ev
idence that it had a deleterious effect on rat islet viability, or function
. Therefore, in isolated adult pig islets, there was a correlation between
iNOS expression and apoptosis, suggesting that iNOS activation may be delet
erious to the adult pig islets. However, other factors such as the fragilit
y of the islet capsule may be equally important. By contrast, fetal pig isl
ets did not express iNOS and this may be an important reason for their enha
nced viability when compared with adult islet tissue.