A Study on Salivary Peptide P-C Like Immunoreactivity in the Human Pancreas, with Special Reference to the Pathogenesis of NIDDM

Previous immunohistochemical study showed that salivary peptide P-C like immunoreactivity, originally isolated from whole human saliva, was present not only in human salivary glands but also in human pancreatic B-cells. To elucidate the pathophysiological role of this peptide-like immunoreactivity in human pancreatic B-cells, immunohistochemical study using antisera against both insulin and peptide P-C was carried out on the paraffin embedded pancreatic tissues of 27 diabetic patients and 30 control subjects.Positive immunofluorescence due to insulin was detected in 96% of the diabetic pancreases and 100% of the controls. A pancreas of only one IDDM did not have any immunofluorescence due to insulin. Thus, no significant differences were seen in connection with the presence of insulin between pancreases of NIDDM and the controls, though the present study did not examine whether the number of pancreatic B-cells in the pancreas of NIDDM was the same as that in the controls or not. In contrast, positive immunofluorescence due to peptide P-C like immunoreactivity was demonstrated in only 41% of the diabetic pancreases but in 87% of the controls. In view of the fact that the diabetic pancreases and the controls were fixed and embedded into paraffin in the same department of pathology and under the same conditions, the negative finding for salivary peptide P-C like immunoreactivity in the diabetic pancreas seems to result neither from the effects of fixatives nor the destructive postmortem effects of enzymes on the antigenicity of peptide P-C like immunoreactivity but from the decreased content of peptide P-C like immunoreactivity in the diabetic pancreas.It has been suggested that Salivary Protein C, the COOH terminal 44 amino acid sequence which is identical to the full sequence of salivary peptide P-C, aids in the maintenance of the calcium concentration in the saliva. If peptide P-C like immunoreactivity in the human pancreatic B-cells is a moiety of Salivary Protein C, it seems likely that peptide P-C like immunoreactivity in the human pancreatic B-cells may play some role in insulin release through the maintenance of the calcium concentration. Based on this hypothesis, the present study leads to the possibility that the failure of insulin release in about 40% of NIDDN may be due to the antecedent decrease in the content of peptide P-C like immunoreactivity in the human pancreatic B-cells. Furthermore, this possibility seems to be supported by the recent immuno-electron microscopic finding that peptide P-C like immunoreactivity was present on the membrane of insulin secretory granules. However, it is still not clear whether the decreased content of peptide P-C like immunoreactivity in the diabetic pancreas is a primary defect or secondary to the metabolic changes following long-term diabetes mellitus.