In this study we report the localisation of PYY immunoreactivity in intestinal mucosa endocrine (EG) cells containing glucagon-related peptides and also in foetal pancreatic A cells of rat and man. Radioimmunoassay of human foetal pancreatic extracts revealed the presence of PYY immunoreactivity, the concentration of which declined with age (from 65.42 pmol/g at week 20 to 17.0 pmol at week 40; correlation coefficient = -0.893), in contrast to the amount of glucagon which remained statistically constant throughout the same foetal period. The identity of this PYY immunoreactive material with the original 36 amino acid porcine peptide has been shown by high pressure liquid chromatography (HPLC).

Temporal changes in non-B cell populations were determined during the period of B cell hyperplasia in diabetes-resistant C57BL/6J mice. Pancreases from normal and db/db mice between 3 and 20 weeks of age were stained immunocytochemically for glucagon, somatostatin and pancreatic polypeptide (PP), and changes in A, D and PP cell volume densities quantified by image analysis. Further, islet volumes, D cell volumes and actual D cell numbers per islet were determined by analysis of serial sections through entire islets. The volume of db/db islets was three- and ten-fold elevated above normal by 8 and 20 weeks, respectively, due mainly to B cell hyperplasia. D cell volume density exhibited a transient increase during the initial phase of B cell hyperplasia, but then showed a gradual reduction; the average number and absolute volume of D cells per islet was comparable in db/db and normal islets from older mice. In contrast, PP cell volume density remained stable throughout, suggesting that this cell type kept pace with B cell hyperplasia. A cells showed a reduced volume density throughout and were distinguished from other islet cells which all responded positively to a degree, albeit non-coordinately, to the mitogenic stimulus exerted by db gene expression. The finding that A cells shared with certain neuroectodermally-derived cell types a differentially high concentration of sn-glycerol-3-phosphate dehydrogenase further underscored the uniqueness of the A cell from other cell types.

An ultrastructural and immunocytochemical study was undertaken to elucidate the temporal and quantitative aspects of the changes occurring in the delta cells in the pancreatic islets of C57BL/KsJ db/db (diabetes) mice. Electron microscopy revealed that prior to the major topographical redistribution of delta cells from their peripheral location to the islet interior, long delta cell filopodial extensions penetrated into the islet, greatly increasing the area of surface contact between delta cells and hypersecretory beta cells. Coincident with delta cells redistribution in islets of 8 to 10 week diabetes mice, the mean number of delta cells per islet had increased significantly. In contrast, their volume density had decreased, indicating incomplete compensation for beta cell hyperplasia which had commenced approximately 4 weeks earlier. In the 14 week mutants, numbers of delta cells per islet and islet volume reached maximum values while delta cell volume density had been restored to a control level. Delta cell volume density exhibited a 2-fold increase in the mutants at 20 weeks that coincided with massive beta cell necrosis. However, a decline in the number of delta cells per islet (173.6 +/- 20.9 at 14 weeks versus 91.2 +/- 20 weeks) suggests that islet degeneration in terminal stages of the syndrome also includes some loss of these cells.