Dissociated insulin and islet amyloid polypeptide secretion from isolated rat pancreatic islets cocultured with human pancreatic adenocarcinoma cells

Abnormal insulin and islet amyloid polypeptide (IAPP) secretion are usually seen in patients with exocrine pancreatic cancer. The p-cell dysfunction i s a characteristic of the glucose intolerance found in pancreatic cancer pa tients. The effects of pancreatic cancer cells on insulin and IAPP secretio n from beta cells are unclear. In this study, isolated rat pancreatic islet s were cocultured with two human pancreatic adenocarcinoma cell lines (Panc -1 and HPAF) and a human colonic adenocarcinoma cell line (HT-29). As a con trol, islets were incubated in the absence of malignant cells. The accumula tion of insulin and IAPP in culture media was measured by radioimmunoassay. Output of insulin and IAPP was decreased in islets cocultured with each ma lignant cell line. Molar ratio of secreted IAPP and insulin (IAPP/insulin) was increased in the islets cocultured with Panc-1 or HPAF cells, but not H T-29 cells. The decreased insulin and IAPP secretion were partly recovered after Panc-1, HPAF, or HT-29 cells were removed. The IAPP/insulin ratio was normalized after the removal of Panc-1 or HPAF cells. This study indicates that insulin and IAPP secretion are altered by the human adenocarcinoma ce lls investigated. The impairment induced by pancreatic adenocarcinoma cells is associated with a hypersecretion of IAPP relative to insulin on a molar basis.