Endocrine Abstracts

D cells comprise 3–10% of the human endocrine pancreas and secrete somatostatin, which inhibits cell proliferation and hormone secretion. Pancreatic tumours secreting somatostatin are associated with the somatostatinoma syndrome, which is characterised by hyperglycaemia, cholethiasis, a low acid output and anaemia. We have examined for the presence of somatostatin secreting cells in pancreatic tumours from a multiple endocrine neoplastic type 1 (MEN1) knockout mouse model, which develops pancreatic endocrine tumours that are mostly insulinomas, as well as parathyroid and pituitary tumours. Mice were kept in accordance with UK Home Office welfare guidelines and project licence restrictions. In order to assess proliferation rates in vivo, drinking water containing BrdU at 1 mg/ml, which becomes incorporated into the DNA of dividing cells, was given to 19–21 month old wild-type (+/+) and Men1 (+/−) littermates for 4 weeks. Pancreatic sections were immunofluorescently labelled with DAPI, somatostatin and BrdU, and 6 islets or pancreatic endocrine tumours from each of four animals per genotype were analysed to determine the percent of somatostatin and BrdU positive cells. The pancreatic islets of wild-type (+/+) mice contained significantly (P<0.001) more somatostatin positive cells than those in the islet cell tumours of MEN1+/− mice (18±2.5 vs 3.5±1.5%, mean±S.E.M). However, the somatostatin containing cells in the islet cell tumours of the MEN1+/− mice had a significantly (P<0.002) higher proliferation rate when compared to the pancreatic islets of wild-type (+/+) mice (0.57±0.25% per day versus 0.01±0.01%). Thus, our findings indicate that somatostatin secreting cells (D-cells) likely comprise ~18% of the normal mouse endocrine pancreas. However, in MEN1+/− pancreatic endocrine tumours, somatostatin containing cells, which have a higher proliferation rate, comprise less than 5% of the cells, and the accompanying reduction in somatostatin secretion may contribute to the observed higher proliferation rate in these tumours.