Thyrotropin-Releasing Hormone and Insulin in Chemically Induced Pancreatic Islet Cell Tumors in Rats

Summary

Thyrotropin-releasing hormone (TRH) and insulin were measured by radioimmunoassay in acetic-acid extracts of 19 pancreatic islet cell tumors induced by streptozotocin and nicotinamide in rats. In addition, gel filtration properties of TRH-immunoreactivity and immunoreactive insulin (IRI) were examined in 5 and 14 tumors, respectively.

TRH was demonstrated in 10 of 19 tumors, with a mean of 166 ± 47 (SEM) pg/mg wet weight, whereas the concentration was less than 3 pg/mg wet weight in the other tumors. In contrast, all tumors contained IRI, with a mean of 11.0 ± 1.6 μg/mg wet weight. Ten tumors in which TRH was demonstrated contained more IRI than those in which TRH was not detected (13.1 ± 1.8 vs 6.5 ± 1.7 μg/mg wet weight, P < 0.02).

After gel filtration, all TRH immunoreactivity was eluted at the same place as synthetic TRH in the 5 tumors. In addition, gel filtration elutes showed essentially the same pattern of IRI in the 14 tumors, with 3 peaks. The predominant IRI peak comigrated with marker insulin (95.7 ± 0.8%), another prominent peak occurred coincident with proinsulin standard (3.3 ± 0.5%), a third peak was present in the void volume (0.28 ± 0.04%). These distributions of IRI were similar to those in extracts of normal pancreases.

The present studies demonstrate TRH immunoreactivity in pancreatic islet cell tumors induced by streptozotocin and nicotinamide in rats. Chemically induced insulinomas can serve as a model for insulin storage which is analogous to islet B cells.

Key-Words

Rat Insulinoma - Streptozotocin - Nicotinamide - Insulin - TRH