Ontogeny of salivary peptide P-C like immunoreactivity in human pancreatic B-cells

Abstract

Abstract. An immunohistochemical study using antisera against proline rich salivary peptide P-C and insulin, glucagon, somatostatin and pancreatic polypeptide antisera was carried out on the foetal pancreas at different stages and on the newborn infant's, infant's, child's and adult pancreas to examine the time at which salivary peptide P-C like immunoreactivity appeared in the human pancreas. Salivary peptide P-C like immunoreactive cells first appeared as a few scattered cells in the foetal pancreas after 16 weeks of gestation and gradually increased in numbers during gestation. The cells corresponded only to insulin immunoreactive cells in the foetal, newborn infant's, infant's, child's and adult pancreas. Only some of the insulin immunoreactive cells in the foetal pancreas contained salivary peptide P-C like immunoreactivity while the majority of those in the infant's pancreas and all those in the child's and adult pancreas did so. The findings, together with the fact that the full sequence of salivary peptide P-C is identical to the COOH-terminal 44 amino acid residues of Salivary Protein C, led to the possibility that peptide P-C like immunoreactivity in the human pancreatic B-cells was not a moiety of the precursor of insulin and pro-insulin, but a moiety of Salivary Protein C. It has been suggested that, in saliva, Salivary Protein C aids in maintenance of the calcium concentration. Based on the hypothesis 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, the present finding seems to explain the fact that the mechanism for insulin release in the foetal pancreas is immature in spite of sufficient biosynthesis of insulin.

Intracellular localization of salivary peptide P-C-like immunoreactivity in the human pancreatic B-cells

“…However, salivary peptide P-C-like im¬ munoreactivity was absent from many insulin se¬ cretory granules of foetal pancreatic B-cells while insulin-like immunoreactivity was seen in all insulin secretory granules. In addition, study of the onto¬ geny of the salivary peptide P-C-like immunore¬ activity in the human pancreatic B-cells (Ito et al 1983b) revealed that salivary peptide P-C-like im¬ munoreactivity first occurred in a few scattered foetal pancreatic B-cells at about the 16th week of gestation while many pancreatic B-cells contained insulin in this stage. These results seem to exclude the possibility that salivary peptide P-C-like im¬ munoreactivity may be a precursor of insulin, since salivary peptide P-C-like immunoreactivity should be constantly demonstrated in the human pancrea¬ tic B-cells which contain insulin if it is a precursor of insulin.…”

“…Since the physiological function of salivary pep¬ tide P-C has not yet been elucidated, it may be inappropriate to speculate about the pathophysio¬ logical role of salivary peptide P-C-like immunore¬ activity in the human pancreas. However, study of the ontogeny of salivary peptide P-C-like immuno¬ reactivity in the human pancreas (Ito et al 1983b) revealed that salivary peptide P-C-like immunore¬ activity was absent from many foetal human pan¬ creatic B-cells in which the insulin releasing mecha¬ nism was known to be immature (Espinosa de los Monteros et Milner et al 1972) and was constantly present in the child and adult pancreatic B-cells in which the insulin releasing mechanism was thought to be mature. In addition, our recent preliminary study (Ito et al 1983c) showed that salivary peptide P-C-like immunoreactivity was too low to be detected in the pancreatic B-cells of some type II diabetic patients by an indirect immuno¬ fluorescence technique while insulin-like immuno¬ reactivity was constantly demonstrated in all pancreata except those of type I diabetes mellitus.…”

“…Thus, the increased occurrence of salivary peptide P-C-like immunoreactivity in each insulin secretory granule may be in parallel with increased detection of foetal pancreatic B-cells containing salivary pep¬ tide P-C-like immunoreactivity at the light micro¬ scopic level. Based on this idea, it seems to require a few months after birth for all insulin secretory granules to have their own function, if they do have such a function, since it was elucidated that pan¬ creatic B-cells containing salivary peptide P-C-like immunoreactivity increased in number during ge¬ station and that it was present in all pancreatic B-cells a few months after birth (Ito et al 1983b).…”

Salivary peptide P-C modulates both insulin and glucagon release from isolated perfused rat pancreas.

“…From ontogenic studies on its occurrence, salivary peptide P-C-like im munoreactivity has been shown to appear in fetal B cells after the 1 6th week of gestation. At the fetal stage before the appearance of salivary peptide P-C, insulin release never occurs, even though insulin biosynthesis has already started in the majority of pancreatic B cells (3). Salivary peptide P-C, however, is a polypeptide having a 44-amino acid se quence that is chemically quite different from insulin and insulin precursors.…”