Inhibition of tumor size by streptozotocin-induced diabetes mellitus

The effects of experimental diabetes mellitus on tumor growth were studied. Male Fischer rats were rendered diabetic with a single intravenous injection of streptozotocin. Ten days later they were inoculated with 10⁶ cells of a methylcholanthrene-induced sarcoma, and tumor growth was observed for 28 days. In three consecutive experiments diabetes selectively inhibited tumor size at Day 28 following inoculation, by 65% (n = 24, P < 0.05), 63% (n = 30, P < 0.001), and 81% (n = 54, P < 0.001) compared to nondiabetic controls. Tumors became palpable in diabetic animals later than in control animals, but palpable tumors grew at a similar rate in the two groups. In diabetic animals with tumors, fasting blood glucose was inversely related to tumor size (r = ?0.80, P < 0.001). This decrease in blood glucose in diabetic animals with large tumors could not be explained by increased insulin or insulin-like activity in serum or tumor extracts. Insulin binding studies to isolated tumor cells showed that tumor cells from diabetic animals had increased numbers of lower-affinity insulin receptors compared to tumor cells from nondiabetic animals. These findings suggest that insulin deficiency or an associated factor in diabetes mellitus causes a marked delay in tumor appearance.