Human insulinoma tissue: in vitro studies of proinsulin/insulin biosynthesis and release.

The rate of proinsulin/insulin turnover has been studied in human insulinoma tissue from ten patients. During the incubation of tumor tissue the ratio of immunoreactive insulin (IRI) release to content was significantly higher than that from isolated human pancreatic islets. The tumor cell cytoplasm (100,000 g supernatant S-100) contained approximately 45% of the IRI. Endogenous proinsulin and insulin were released throughout the incubation. Newly synthesized proinsulin was detected in the 15 min pulse microsomal, secretory granule, S-100 and media samples. These results suggest that defective hormonal storage and release mechanisms are operative in human insulinoma cells resulting in a higher turnover of proinsulin and insulin compared with pancreatic islet tissue.