Induction of Glucagon Synthesis in Diabetic CBA Mice Bearing

ABSTRACT-Passaging of the mammary aplastic carcinoma several times In diabetic CBA mice Induced an extrapancreatlc secretion of glucagon. Consequently,_lhe concentration of Immu-noreactive glucagon was higher In plasma and the tumor tissue extract. After the In/ectlon of alloxan, attempts to reduce the level of this hormone In the diabetic mice were unsuccessful. The tumor cells could have been responsible for the secretion of glu-cagon.-JNCI 63: 1005-1008, 1979. The growth of some tumors has been shown to be influenced by pancreatic hormones. Also, some tumors produce either insulin-like substances (1-5), soma to-medin (6), or some unidentified factors that stimulate the growth of normal tissues, tumor tissues, or both (7-9). A transplantable mammary aplastic carcinoma of mice used in this study was adaptable to the diabetic conditions hypoinsulinemia and hypoglucagonemia (4), possibly because tumor cells secrete insulin or because these cells were selected through the passages in dia-betic recipients (10). Secretion of insulin and its function are diminished by the secretion of the antagonist glucagon. We de-cided to determine whether the passage of tumor 'tissue in diabetic recipients could induce the secretion of glu-cagon. MATERIALS AND METHODS Inbred male CBA mice 4 months old were kept in plastic cages and supplied with pelleted food and tap water ad libitum. The mammary aplastic carcinoma, which was de-veloped spontaneously in a CBA mouse in back of the mammary region (4), has been maintained in the CBA strain by serial im transplantation of lXI06 cells into the flank. Suspensions of tumor cells were prepared and counted by a standard technique (11). The original morphology of the tumor did not change during these experiments. Crystalline insulin diluted in physiologic saline (Pliva, Zagreb, Yugoslavia) was injected im daily: 4 IV into diabetic mice or 2 IV into nondiabetic mice