Effects of insulin on melanoma and brain metabolism

Abstract

Both brain and melanoma slices displayed similar Q O 2 CO 2 values, but marked differences occurred in Q N 2 CO 2 under certain conditions. Thus, the two tissues responded differently to added magnesium, phenol, and insulin. The first two substances markedly increased the Q N 2 CO 2 of brain but slightly inhibited that of melanoma. The Q N 2 CO 2 of brain slides was not increased by insulin but that of melanoma was ( ca. 40%). As little as 0.003 mg (0.1 units) of crystalline zinc-insulin per ml was sufficient to give maximal stimulation. Crystalline zinc-insulin freed of hyperglycemic factor was as effective as regular crystalline zinc-insulin in increasing the Q N 2 CO 2 of melanoma slices. Hyperglycemic factor largely freed of insulin had no appreciable effect on Q N 2 CO 2 . Zinc appears to play a critical role in connection with the influence of insulin on Q N 2 CO 2 of melanoma slices. The relative concentrations of the two substances are critical. Under aerobic conditions insulin variably increased the R.Q., Q O 2 CO 2 , and absolute Pasteur effect of melanoma. Q O 2 (respiration) was never increased, but was sometimes decreased. Exposure of melanoma-bearing mice to 35° or 40° C, for 13 hours or more, was associated with a marked diminution in the Q N 2 CO 2 of the tumor slices as compared to tumor slices from mice exposed to ca. 20° C. Insulin increased (average 49%) the Q N 2 CO 2 of slices from the heat-treated tumors to a level approximately equal to that of slices from 20° C tumors where insulin gave only slight stimulation (average 7%); additional (12 to 44 days) exposure to 35° or 40° C resulted in marked suppression of tumor growth and further decline in the Q N 2 CO 2 .