Tissue kallikreins are thought to be present in the pancreatic islets of Langerhans and to aid in the conversion of
proinsulin to
insulin. In recent immunohistochemical studies, we observed strong staining of the newly identified human
kallikreins 6 and 10 (hK6 and hK10) in the islets of Langerhans. Here, we examine hK6 and hK10 immunoexpression in different types of islet cells of the endocrine pancreas, in order to obtain clues for hK6 and hK10 function in these cells. Ten cases of normal pancreatic tissue, two cases of
nesidioblastosis, five
insulin-producing tumours and one case of
multiple endocrine neoplasia 1 syndrome, containing an
insulin-, a
somatostatin- and several
glucagon-producing tumours, as well as tiny foci of endocrine dysplasia with different predominance of the secreted
hormones (mainly
glucagon and
pancreatic polypeptide) were included in the study. A
streptavidin--
biotin--
peroxidase and an
alkaline phosphatase protocol, as well as a sequential immunoenzymatic double staining method were performed, using specific
antibodies against hK6, hK10,
insulin,
glucagon,
somatostatin,
pancreatic polypeptide, and
serotonin. hK6 and hK10 immunoexpression was observed in the islets of Langerhans, including the
pancreatic polypeptide-rich islets, in the normal pancreas. Scattered hK6 and hK10 positive cells were localized in relationship with pancreatic acinar cells. In the exocrine pancreas, a cytoplasmic and/or brush border hK6 and hK10 immunoexpression was observed in the median and small sized pancreatic ducts, while the acinar cells were negative. Foci of
nesidioblastosis and endocrine dysplasia expressed both
kallikreins. hK6 and hK10 were also strongly and diffusely expressed throughout all
insulin-,
glucagon- and
somatostatin-producing tumours. The double staining method revealed co-localization of each
hormone and hK6/hK10 respectively, in the same cellular population, in the normal as well as in the diseased pancreas. Our results support the view that hK6 and hK10 may be involved in
insulin and other pancreatic
hormone processing and/or secretion, as well as in physiological functions related to the endocrine pancreas.