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Protein kinase C [cPKC: α, β (βI βII), γ], a Ca2+- and phospholipid-dependent enzyme, has been thought to play a critical role in the synthesis and secretion of gut hormones in gastrointestinal mucosa. However, the localization of PKC has not yet been clarified at the cellular level in the gastrointestinal epithelium. The present study was made to identify cPKC-containing cells immunohistochemically in the rat duodenal epithelium by light and electron microscopy and by confocal laser scanning microscopy. Special attention was paid to the demonstration of cPKC in basal granulated cells. By light microscopy, some duodenal epithelial cells were demonstrated to be immunopositive for PKC α-, β- and γ-subspecies. Their distribution and incidence were almost similar to those of cells stained by the silver impregnation method of Grimelius. By electron microscopy, profiles of secretory granules were found at the basal region of the PKC-immunopositive epithelial cells. When the cells were double-immunostained for gastrin, serotonin or somatostatin and for PKC α-, β- or γ-subspecies, these gut hormones and PKC subspecies were shown to colocalize as examined by confocal laser scanning microscopy. These findings show that cPKC (α, β, γ) is present in basal granulated cells such as G-, EC- and D-cells, presumably playing some important role in regulation of gut hormones, including their synthesis and/or secretion.

In this report, we briefly present the case of a 67-year-old woman who developed recurrent glucagonoma with lymph node metastasis. An immunohistochemical study of the metastatic tumor revealed immunoreactivity of glucagon and protein kinase C (PKC)-alpha, -beta, and -gamma in the tumor cells, two types of which were seen by electron microscopy. One type had abundant secretory granules and mitochondria, while the other had few granules and mitochondria. Some granules were similar to typical A cell granules and others were atypical. An immunoelectron microscopic demonstration revealed PKC-alpha, -beta, and -gamma immunostaining in the cytoplasm of all the tumor cells, while some secretory granules had PKC immunostaining, and others had no immunostaining. Thus, it appears that metastatic glucagonoma and its associated granules are composed of two types of mature and immature cells or granules. As immunoreactivity of PKC-alpha and -gamma was found in the tumor cells, but not in the normal A cells of the islets of Langerhans, the PKC subspecies alpha and gamma, which are not present in normal pancreatic A cells, may exist in human glucagonoma cells.