Abstract:
Cells of the pancreatic islets produce several molecules including insulin (beta cells),
glucagon (alpha cells), somatostatin (delta cells), pancreatic polypeptide (PP cells),
ghrelin (epsilon cells), serotonin (enterochromaffin cells), gastrin (G cells) and small
granules of unknown content secreted by the P/D1 cells. Secretion mechanism of
some of these molecules is still poorly understood. However, Cathepsin L is shown
to regulate insulin exocytosis in beta cells and activate the trypsinogen produced by
the pancreatic serous acini cells into trypsin. The structure of the propeptide region
of Cathepsin L is homologous to Cytotoxic T-lymphocyte antigen-2 alpha (CTLA-2
alpha) which is also shown to exhibit selective inhibitory activities against Cathepsin
L. It was thought that if CTLA-2 alpha was expressed in the pancreas; then, it would
be an important regulator of protease activation and insulin secretion. The purpose
of this study was, therefore, to examine by immunohistochemistry the cellular localization
and distribution pattern of CTLA-2 alpha in the pancreas. Results showed that
strong immunoreactivity was specifically detected in the pancreatic islets (endocrine
pancreas) but not in the exocrine pancreas and pancreatic stroma. Immunostaining
was further performed to investigate more on localization of Cathepsin L in the pancreas.
Strong immunoreactivity for Cathepsin L was detected in the pancreatic islets,
serous cells and the pancreas duct system. These findings suggest that CTLA-2
alpha may be involved in the proteolytic processing and secretion of insulin through
regulation of Cathepsin L and that the regulated inhibition of Cathepsin L may have
therapeutic potential for type 1 diabetes.
