Degradation of insulin and glucagon by a factor associated with Walker 256 carcinosarcoma cells

Earlier studies from this laboratory reported that, in rats bearing the Walker 256 carcinosarcoma, circulating insulin levels were significantly reduced relative to non-tumor-bearing rats. The present study extends this observation to include a significantly (P less than 0.01) reduced plasma level of glucagon in rats bearing the tumor for both 7 and 10 days. In order to determine if the tumor itself somehow plays a role in the degradation of these protein hormones, either cultured Walker 256 tumor cells (in the case of the insulin studies) or cells from freshly excised tumor (for the glucagon studies) were incubated with 125I-labeled insulin or glucagon. Following the incubation period, the amount of TCA-precipitable radio-label remaining in the incubation medium was markedly reduced after exposure to cells. This suggests that the tumor cells have the capability of degrading both insulin and glucagon. In a separate series of experiments, it was found that medium, in which freshly excised tumor cells had been incubated previously and then discarded, retained a substance which degraded 125I-labeled glucagon and that this degradation of glucagon could be blocked by co-incubation with aprotinin, a protease inhibitor.